Encyclopedia Of Animal Science - O ppsx

Omega-3 and -6 Fatty Acids Brian K Speake Peter F Surai Scottish Agricultural College, Ayr, U.K INTRODUCTION Dietary Sources and Interconversions Dietary fatty acids were originally thought to perform rather passive roles as a source of energy and cell membrane components This view has now been transformed by the realization that omega-3 and omega-6 polyunsaturates are potent determinants of the body’s physiological state, regulating fuel partitioning, inflammation, and neurological function and are, therefore, crucial determinants of health, disease, and productivity Common dietary sources of the various polyunsaturated fatty acids are shown in Table Vertebrate animals can synthesize saturated and monounsaturated fatty acids from dietary carbohydrate but are unable to synthesize 18:2o6 or 18:3o3 These polyunsaturates must, therefore, be provided in the diet and are referred to as essential fatty acids Animals can, however, convert 18:2o6 to 20:4o6 via the action of desaturase and elongase enzymes.[1] The same enzymes are involved in the conversion of 18:3o3 to 20:5o3 and 22:6o3 This ability to synthesize C20 and C22 polyunsaturates from their C18 precursors varies greatly among animal species Vertebrate animals are unable to perform interconversions between the o6 and o3 series.[1] GENERAL ASPECTS Structures and Nomenclature A fatty acid molecule consists of a hydrocarbon chain with an acidic carboxyl group at one end and a terminal methyl group at the other In the case of a saturated fatty acid, all the carbon atoms in the chain are linked by single bonds, whereas an unsaturated fatty acid is defined by the presence of one or more double bonds in the chain Most polyunsaturated fatty acids of animal tissues belong to either the omega-6 (o6) or omega-3 (o3) series (also referred to as n-6 and n-3, respectively) These terms indicate the positioning of the double bonds in the chain Thus, for an o6 fatty acid, the double bond nearest to the methyl end is located between carbon atoms and 7, counting from the methyl terminus Similarly, the double bond nearest to the methyl end of an o3 fatty acid forms the link between carbon atoms and Fatty acids are symbolized by a shorthand nomenclature For example, linoleic acid is abbreviated to 18:2o6, indicating a chain length of 18 carbon atoms with double bonds, the first double bond being located between carbons and from the methyl end Other polyunsaturated fatty acids with important functions in animals are a-linolenic (18:3o3), arachidonic (20:4o6), eicosapentaenoic (20:5o3), and docosahexaenoic (22:6o3) acids In the diets and tissues of animals, fatty acids are mainly present in the esterified form, as triacylglycerols, phospholipids, or cholesteryl esters, with only traces occurring in the free (unesterified) form Encyclopedia of Animal Science DOI: 10.1081/E EAS 120019738 Copyright D 2005 by Marcel Dekker, Inc All rights reserved Functions and Health Benefits Skin lipids (ceramides) that contain 18:2o6 perform a specific function in preventing transepidermal water loss Dietary vegetable oils that are rich in 18:2o6 tend to reduce plasma cholesterol, probably by stimulating the hepatic uptake of low-density lipoprotein Polyunsaturated fatty acids perform major roles as components of membrane phospholipids, where the degree of unsaturation is a key determinant of the biophysical properties of the membrane Very high proportions of 22:6o3 are present in the phospholipids of neuronal cells of the brain and of the rod photoreceptor cells of the retina.[2] Optimal functional development of the neural tissues is dependent on adequate provision of 22:6o3 during fetal and neonatal life Mammalian sperm phospholipids also display high proportions of 22:6o3, presumably to enhance the flexibility of the sperm tail membranes.[3] Polyunsaturates, particularly 20:5o3 and 22:6o3, are powerful regulatory molecules By interacting with specific transcription factors (PPARa, SREBP-1, NF-Y), they alter the pattern of gene expression in liver cells, profoundly altering the concentrations of key metabolic enzymes.[1] These changes increase the b-oxidation of fatty acids and simultaneously inhibit the synthesis of fatty acids and triacylglycerol, thereby reducing 681 682 Omega-3 and -6 Fatty Acids Table Omega and fatty acids: Dietary sources and metabolic functions Name Dietary sources Functions Linoleic 18:2o6 a linolenic 18:3o3 Arachidonic 20:4o6 Plant seed oils (e.g., sunflower, safflower, maize) Green leaves, flaxseeds, linseed oil Meat, eggs Eicosapentaenoic 20:5o3 Oily fish, seafood Docosahexaenoic 22:6o3 Oily fish, seafood Energy source; skin lipids; precursor of 20:4o6 Energy source; precursor of 20:5o3 and 22:6o3 Membrane structure; signal transduction; gene expression; fuel partitioning; precursor of eicosanoids; proinflammatory Gene expression; fuel partitioning; precursor of eicosanoids; anti inflammatory; cardiovascular protection Membrane structure; brain, retina and sperm function; gene expression; fuel partitioning; anti inflammatory; cardiovascular protection (Based on information from Refs 5.) lipoprotein secretion Thus, dietary fish oils can reduce plasma lipids and inhibit the accumulation of body fat.[1] Polyunsaturates also regulate cell function as a result of their conversion to eicosanoids (prostaglandins, thromboxanes, leukotrienes).[1] Eicosanoids derived from 20:4o6 are generally more proinflammatory and prothrombotic than those derived from 20:5o3 Dietary fish oil reduces inflammation and thrombosis by antagonising the production and action of the o6-derived eicosanoids.[4] The hypolipidemic, anti-inflammatory and antithrombotic effects of o3 fatty acids, plus their antiarrhythmic and antihypertensive properties, explain the protective effects of dietary fish oil against cardiovascular disease Beneficial effects of o3 fatty acids in the prevention or treatment of rheumatoid arthritis, autoimmune diseases, cancers, and mental disorders have also been reported.[4] RELEVANCE TO ANIMAL SCIENCE Enhancing the o3 Content of Animal Products to Benefit the Health of Consumers During human evolution, our metabolism became adapted to a hunter-gatherer diet that provided a balanced intake of o6 and o3 fatty acids in a ratio of about 1:1 In the Western world, this ratio may currently be as high as 20:1.[5] Livestock raised on grain display much higher o6:o3 ratios in their tissues compared with meat from animals in the wild.[5] In the case of monogastric livestock, the o3 status of their tissues is easily improved by providing a source of these fatty acids in their diets Thus, dietary supplementation of pigs and poultry with fish oil, fish meal, flaxseed, or certain algae readily enhances the concentration of o3 fatty acids in the lipids of pork, chicken meat, and eggs.[5] Modulation of the fatty acid composition of ruminant meat and milk is restricted by the extensive biohydrogenation of polyunsaturates that occurs in the rumen This problem can be partially circumvented by encapsulation of oil supplements in a protective coating to prevent access by rumen microbes.[6] Also, there is some evidence that 20:5o3 and 22:6o3 are less susceptible to biohydrogenation in comparison with 18:2o6 and 18:3o3 Although supplementation of dairy cows with fish oil (nonencapsulated) increases the proportions of o3 fatty acids in milk lipid, it is difficult to achieve concentrations of 22:6o3 greater than 0.1% of milk fatty acids due to the low efficiency (3%) of transfer of this fatty acid from diet to milk.[7] Fish oil supplements result in increased concentrations of trans-fatty acids and conjugated linoleic acid in milk and also depress milk fat content.[7] Intake of linseed or fish oil by cattle produced significant increases in the concentrations of o3 fatty acids in muscle phospholipid.[6] Cattle fed on grass have higher concentrations of o3 fatty acids in muscle lipids compared with cattle raised on concentrates Improving the Health and Productivity of Livestock Despite the massive amount of research on the role of polyunsaturates in human health, the potential for improving the health of livestock by dietary fatty acids has received limited attention Formulated animal feeds usually have a very high o6:o3 ratio and often contain no 22:6o3 Recent work has highlighted some potential benefits of o3 supplementation for the health and Omega-3 and -6 Fatty Acids productivity of the animal For example, supplementation of sows with fish oil during pregnancy increased both the 22:6o3 content and the weight of the piglet brain.[8] These changes were associated with a decrease in preweaning mortality, largely by a reduction in the number of piglets crushed by the sow, and possibly reflecting improved cognitive development during fetal life.[8] Supplementation of boars and cockerels with fish oil improved fertility by increasing the 22:6o3 content, number, and fertilizing ability of spermatozoa.[3] Chickens that were fed diets rich in either o3 or o6 fatty acids displayed major reductions in both plasma triacylglycerol and in the weight of the abdominal fat pad compared to birds on a tallow-rich diet.[9] 683 REFERENCES CONCLUSION With lipids occupying center stage in the relation between diet and human health, enhancing the o3 content of meat, milk, and eggs is regarded as desirable Furthermore, the potential to improve the health and productivity of livestock by dietary fatty acids is beginning to be evaluated ACKNOWLEDGMENT We are grateful to the Scottish Executive Environment and Rural Affairs Department for financial support Nakamura, M.T.; Cho, H.P.; Xu, J.; Tang, Z.; Clarke, S.D Metabolism and functions of highly unsaturated fatty acids: An update Lipids 2001, 36 (9), 961 964 Salem, N., Jr.; Litman, B.; Kim, H K.; Gawrisch, K Mechanisms of action of docosahexaenoic acid in the nervous system Lipids 2001, 36 (9), 945 959 Speake, B.K.; Surai, P.F.; Rooke, J.A Regulation of Avian and Mammalian Sperm Production by Dietary Fatty Acids In Male Fertility and Lipid Metabolism; De Vriese, S.R., Christophe, A.B., Eds.; AOCS Press: Champaign, IL, 2003; 96 117 Lands, W.E.M Diets could prevent many diseases Lipids 2003, 38 (4), 317 321 Simopoulos, A.P New products from the agri food industry: The return of n fatty acids into the food supply Lipids 1999, 34 (Supplement), S297 S301 Wood, J.D.; Enser, M.; Fisher, A.V.; Nute, G.R.; Richardson, R.I.; Sheard, P.R Manipulating meat quality and composi tion Proc Nutr Soc 1999, 58 (2), 363 370 Offer, N.W.; Marsden, M.; Dixon, J.; Speake, B.K.; Thacker, F.E Effect of dietary fat supplements on levels of n polyunsaturated fatty acids, trans acids and conjugated linoleic acid in bovine milk Anim Sci 1999, 69 (3), 613 625 Rooke, J.A.; Sinclair, A.G.; Edwards, S.A.; Cordoba, R.; Pkiyach, S.; Penny, P.C.; Penny, P.; Finch, A.M.; Horgan, G.W The effect of feeding salmon oil throughout preg nancy on pre weaning mortality of piglets Anim Sci 2001, 73 (3), 489 500 Newman, R.E.; Bryden, W.L.; Fleck, E.; Ashes, J.R.; Buttemer, W.A.; Storlien, L.H.; Downing, J.A Dietary n and n fatty acids alter avian metabolism: Metabolism and abdominal fat deposition Br J Nutr 2002, 88 (1), 11 18 Ontogeny: Adipose Tissue Gary J Hausman United States Department of Agriculture, Agricultural Research Service, Athens, Georgia, U.S.A D B Hausman University of Georgia, Athens, Georgia, U.S.A INTRODUCTION Adipose tissue, now considered an endocrine organ, secretes or expresses many potential endocrine factors, including leptin and insulin-like growth factor (IGF) system proteins Therefore, the structrual and functional aspects of adipose tissue ontogeny are important to the growing and mature animal for goats, is generally found only in internal fat depots Bovine SQ originates as BAT to a degree but soon converts to WAT At birth, sheep and cattle BAT and WAT have a mature morphology since these tissues are virtually filled with adipocytes (Table 1) BAT rapidly transforms to WAT in neonatal ruminants during the neonatal period (Table 1) POSTNATAL DEVELOPMENT FETAL AND NEONATAL DEVELOPMENT Fat cell development commences by midgestation and is characterized by the appearance of a number of fat cell clusters, or primitive organs, which subsequently increase in number and size throughout fetal development (Table 1).[1–3] Primitive fat organs are vascular structures in presumptive adipose tissue with few or no fat cells (Fig 1; Table 1) Fetal adipocyte development is spatially and temporally related to capillary development.[2] Although angiogenesis appears to be linked to adipogenesis, the major regulators of angiogenesis have not been examined in meat animal adipose tissue (Table 2) Subcutaneous (SQ) depots develop before internal depots in chickens, cattle, and sheep, whereas the middle SQ layer and internal depots develop concurrently in pigs Subcutaneous adipose tissue layers are established at the onset of adipose development and have distinct fetal and postnatal developmental patterns.[1,5] Brown adipose tissue (BAT) is responsible, in part, for nonshivering thermogenesis in the neonate Brown adipocytes contain more elaborate and differentiated mitochondria (Table 1)[4] than multilocular adipocytes in developing white adipose tissue (WAT; Table 1) BAT is characterized by expression of uncoupling protein (UCP-1), a mitochondrial transport protein responsible for BAT heat production Leptin gene expression effectively marks white adipocytes since it is positively correlated with the unilocular cell morphology but inversely related to UCP-1 expression Leptin influences many physiological processes and is primarily synthesized and secreted by WAT BAT has not been detected in pigs and chickens but is present in neonatal ruminants and, except 684 WAT predominates in postnatal animals and adipocyte development is depot- and species-dependent (Table 3).[5–7] Adipocytes in internal depots are larger than those in the intramuscular depot, and adipocyte hypertrophy is largely responsible for fat accretion of most depots (Table 3) Generally, fat cell hypertrophy is associated with increased leptin gene expression In the SQ depot, leptin expression responds to fasting and hormones associated with the onset of puberty.[8,9] Leptin expression traits distinguish adipose depots in sheep and cattle (Table 3) ADIPOSE TISSUE EXPRESSION OF TRANSCRIPTION, METABOLIC, AND REGULATORY FACTORS Adipose cell differentiation is accompanied by transcriptional activation of genes by several groups of transcription factor proteins: PPARg, C/EBPs and ADDI/SREBP-1 (Table 2) C/EBPa, b, and PPARg were expressed early and throughout fetal pig adipose tissue development.[3] The expression levels of several transcription factors and associated adipogenic genes increase neonatally and expression of the stearoyl coenzyme A desaturase (SCD) gene rapidly increases postnatally in several species (Table 2) HORMONAL REGULATION OF ADIPOSE TISSUE DEVELOPMENT AND METABOLISM Fetal hypophysectomy (hypox) increases SQ adipose tissue accretion in fetal sheep and pigs, and increases Encyclopedia of Animal Science DOI: 10.1081/E EAS 120019739 Copyright D 2005 by Marcel Dekker, Inc All rights reserved Ontogeny: Adipose Tissue 685 Table Characteristics of fetal and neonatal adipose tissue development WAT Fetal Key developmental traits Mode of accretion or expansion Molecular and ultrastructural markers Late fetal tissue and adipocyte morphology Neonatal Tissue and adipocyte morphology Mode of accretion or expansion Accretion or expansion rate Molecular and ultrastructural markers cattle (C), pigs (P), and sheep (S) Depot dependent development of primitive fat organs and structural differentiation of presumptive fat tissue C and S: hyperplasia and hypertrophy; P: hyperplasia with less hypertrophy Leptin; few and simple mitochondria Moderately vascular, mature (C,S) or immature (P) tissue with either unilocular and multilocular cells (C,S) or smaller multilocular cells (P) Mature tissue with unilocular cells (C, P) or multilocular and unilocular cells (S) Depot dependent hyperplasia and hypertrophy Rapid Expression of leptin, transcription factors, and lipogenic enzymes BAT cattle (C), sheep (S), and goats (G) Depot dependent development of primitive fat organs Hyperplasia and hypertrophy UCP 1; mitochondria proliferation and differentiation Very vascular, mature tissue with unilocular and multilocular cells Mature tissue with unilocular cells (C) or cells transforming from multilocular to unilocular (S) Hypertrophy Relatively slow BAT to WAT conversion : Decreased UCP expression and structural and functional mitochondrial degradation Abbreviations: UCP uncoupling protein, WAT white adipose tissue, BAT brown adipose tissue Fig Phosphatase histochemistry in cryostat sections of fetal perirenal adipose tissue from 70 day (A), 90 day (B) and 105 day (C, D) fetal pigs Note that phosphatase reactivity is limited in arterioles (arrows) in perirenal tissue at 70 days (A), whereas more extensive phosphatase reactivity indicates that arteriolar differentiation (arrows) has clearly progressed by 90 (B) and 105 days (C, D) Areas within perirenal tissue at 90 days (B, arrowheads) can be considered primitive fat organs since there are few to no fat cells but the areas are otherwise morphologically similar to adipocyte filled areas (a) of adipose tissue at 105 days (C) A, B, C Â 300; D Â 150 686 Ontogeny: Adipose Tissue Table Collective reports of genes and proteins expressed during adipose tissue ontogeny Regulatory Fetal WAT pigs (P) and cattle (C) BAT cattle BAT and WAT sheep and goats Neonatal WAT pigs (P) and cattle (C) BAT cattle BAT and WAT sheep and goats Postnatal Pig WAT Cattle WAT Sheep WAT P: leptin,OBLR, IGFBP 1, 2, 3, 4, 5, IGF I, II, TGF b, adipsin; C:UCP UCP 1, b ARs Leptin, UCP 1, PRLR1, P: leptin,UCP 2, 3, GHR, IGF I, II ;C :PREF1, b ARs UCP 1,a b ARs Leptin, UCP 1,a GR, ANG II receptors 1, Leptin, OBLR, EGF IGFBP 1, 3, bFGF, HGF, GHR, IGF I, II, IGF IR, b ARs, adipsin Leptin, Dlk C 2, PREF1,a UCP 1,a IGF 1,NAT1, TNFa, heat shock 70 kDa protein Leptin, OBRL, UCP Metabolism Transcription factors P: C/EBPa, b and &, PPARg Cytochrome c oxidase, ADP/ ATP carrier GAPDH,VDAC, ADP/ATP carrier, cytochrome c oxidase P:GLUT 4,HSL, LPL,SCD, aP2; C:GLUT 1,SCD, LPL P: C/EBPa, b and &, PPARg, ADD1 Cytochrome c oxidase, ADP/ ATP carrier 11 b HSD 1, 2, cytochrome c oxidase, ADP/ATP carrier, GLUT SCD, ACC, ACO, FAS, LPL, ME, GLUT 1, GLUT ADD1, SREBP 1, SREBP 2, PPARg, PPARa, C/EBPa, C/EBP b SCD, GLUT 4, HSL GLUT 1, LPL, ACC, ATP citrate lyase, VDAC, GDH, FAS PPARg 1, SCD, ACC, FAS, LPL, HSL PPARg Abbreviations: ADD1 adipocyte determination and differentiation dependent factor 1, PPAR peroxisome proliferator activated receptor, C/ EBP CCAAT enhancing binding protein, SREBP sterol regulatory element binding protein, FAS fatty acid synthase, ACO acyl CoA oxidase, EGF epidermal growth factor, bFGF basic fibroblast growth factor, TGF transforming growth factor, TNF tumor necrosis factor, HGF hepatocyte growth factor, GLUT glucose transport protein, IGFBP insulin like growth factor binding protein, IGF insulin like growth factor, IGF 1R IGF receptor, GHR growth hormone receptor, OBR long form leptin receptor, HSL hormone sensitive lipase, LPL lipoprotein lipase, UCP uncoupling protein, 11 b HSD 11 beta hydroxysteroid dehydrogenase, SCD stearoyl coenzyme A desaturase, ME malic enzyme, b ARs beta adrenergic receptors, PREF1 preadipocyte factor 1, GDH glutamate dehydrogenase, GAPDH glyceraldehyde phosphate dehydrogenase, aP2 fatty acid binding protein, ACC acetyl CoA carboxylase, ANG II angiotensin, VDAC voltage dependent anion channel, and NAT1 novel APOBEC target a Undetectable Additional genes/proteins reported: Postnatal pig adipose; low density lipoprotein receptor, low density lipoprotein related protein and high density lipoprotein binding protein; postnatal cattle WAT type III collagen and ribosomal proteins; fetal pig adipose laminin and type IV collagen Table Characteristics of postnatal adipose tissue development Postnatal depots Internal Subcutaneous Intramuscular/ intermuscular Adipocyte size Mode of accretion or expansion Largest Early: hyperplasia and hypertrophy; later: primarily hypertrophy Species dependent Intermediate Early: hyperplasia and hypertrophy; later: hypertrophy and species dependent hyperplasia Dependent on location, layer and species Highest High to moderate and increased by fasting Smallest Primarily hyperplasia with little hypertrophy Accretion and accretion rate Lipogenesis Leptin gene expression basal and response to fasting Intermediate Omental: moderate and increased by fasting; Perirenal: species dependent Slow Lowest Very low and not changed by fasting Ontogeny: Adipose Tissue fat cell size and lipogenesis in fetal pig adipose tissue Hormone-sensitive adipogenesis begins on approximately day 70 of fetal life.[1] Hydrocortisone and thyroxine (T4) are critical for cellular and vascular development in fetal pig adipose tissue In contrast, T3 and cortisol are critical for establishing BAT functionality, including UCP protein expression, in fetal sheep Growth hormone (GH) decreases lipid deposition in fetal sheep and pigs and reduces fat cell size in fetal pigs Adipose tissue IGF-1 and IGFBPs mediate chronic hormone effects on adipose development in fetal, neonatal, and postnatal animals, and influence the onset of fetal pig SQ adipocyte development (Table 2).[10] Expression and secretion of IGF-1 and IGFBPs by adipose tissue increase with fetal age, and many components of the IGF-GH system are expressed by postnatal pig adipose tissue (Table 2) 687 leptin expression to fasting and other modulators as influenced by depot and species Furthermore, there is little to no information on the ontogeny of adipocyte expression of other regulatory factors expressed and secreted by rodent and human adipocytes REFERENCES ONTOGENY AND REGULATION OF FETAL ADIPOSE TISSUE LEPTIN GENE EXPRESSION Leptin gene expression in adipose tissue is developmentally regulated in fetal sheep and fetal pigs.[8] Together, hydrocortisone and T4 markedly stimulate leptin expression in fetal pigs with no influence on serum leptin levels Insulin but not cortisol stimulates leptin gene expression in fetal sheep adipose as it does in growing animals CONCLUSION The cellular and functional aspects of WAT and BAT ontogeny have been studied, including examination of expression of the WAT marker gene (leptin), the BAT marker gene (UCP-1), and a number of other genes associated with WAT and BAT development The ontogeny and regulation of adipose tissue leptin gene expression have been examined.[8,9] Additional studies are necessary to determine the ontogeny of the response of 10 Hausman, G.J.; Hausman, D.B Endocrine Regulation of Porcine Adipose Tissue Development: Cellular and Metabolic Aspects In Growth of the Pig; Hollis, G.R., Ed.; CAB International: Wallingford, UK, 1993; 49 74 Crandall, D.L.; Hausman, G.J.; Kral, J.G A review of the microcirculation of adipose tissue: Anatomic, metabolic, and angiogenic perspectives Microcirculation 1997, 4, 211 232 Martin, R.J.; Hausman, G.J.; Hausman, D.B Regulation of adipose cell development in utero Proc Soc Exp Biol Med 1998, 219, 200 210 Cinti, S Anatomy of the adipose organ Eat Weight Disord 2000, 5, 132 142 Allen, C.E.; Beitz, D.C.; Cramer, D.A.; Kaufman, R.G Biology of Fat in Meat Animals; North Central Regional Research Publication, University of Wisconsin: Madison, 1976; Vol 234 Hood, R.L Relationships among growth, adipose cell size, and lipid metabolism in ruminant adipose tissue Fed Proc 1982, 41, 2555 2561 Cartwright, A.L Adipose cellularity in Gallus domesticus: Investigations to control body composition in growing chickens J Nutr 1991, 121, 1486 1497 Barb, C.R.; Hausman, G.J.; Houseknecht, K.L Biology of leptin in the pig Domest Anim Endocrinol 2001, 21, 297 317 Chilliard, Y.; Bonnet, M.; Delavaud, C.; Faulconnier, Y.; Leroux, C.; Djiane, J.; Bocquier, F Leptin in ruminants Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration Domest Anim Endocrinol 2001, 21, 271 295 Hausman, D.B.; DiGirolamo, M.; Bartness, T.J.; Hausman, G.J.; Martin, R.J The biology of white adipocyte proliferation Obes Rev 2001, 2, 239 254 Ontogeny: Muscle Jan E Novakofski Robert H McCusker Suzanne Broussard University of Illinois, Urbana, Illinois, U.S.A INTRODUCTION Formation of skeletal muscle is called myogenesis Precursor cells called myoblasts originate in the somitic mesoderm Limb and abdominal muscles develop from myoblasts migrating out of somites, whereas back muscles develop from nonmigrating myoblasts Multinucleated skeletal muscle cells are formed from fusion of mononucleated myoblasts into myotubes Subsequent synthesis of contractile myofibrils and organization into sarcomeres within myotubes result in maturation into myofibers Myogenesis occurs in a primary wave during embryonic development followed by a secondary wave during early fetal developments Primary and secondary fibers are predisposed to form slow and fast contraction fibers, respectively Innervation occurs concurrently with maturation of muscle fibers and subsequently plays an important role in survival and determination of myofiber type Groups of myofibers separate into individual muscles surrounded by connective tissue as development continues Myofiber number becomes fixed near birth, although additional myonuclei are added as the fibers enlarge Nuclei are added to existing fibers by fusion of additional myoblasts called satellite cells Myofibers grow in diameter by adding new circumferential contractile filaments and grow in length by adding new sarcomeres to the end of existing filaments Postnatal development of contractile and metabolic properties involves sequential replacement of many fiber-type specific proteins within existing myofibers Myoblast differentiation is accompanied by cell-cycle withdrawal followed by fusion to form myotubes with central nuclei Contractile protein accumulation, displacement of nuclei to the periphery, and innervation result in maturation of myofibers Embryonic myoblasts differentiate to form primary muscle fibers in early gestation, before individual muscles can be discerned Fetal myoblasts use the surface of primary myofibers as a scaffold to align and form secondary fibers In mammals, all primary fibers are initially slow fibers with some becoming fast fibers in fast twitch muscles Most secondary fibers are initially fast fibers Since there are to 20 times more secondary than primary fibers, this gives rise to a common histological pattern of a small number of slow fibers surrounded by a larger number of fast fibers The majority of myofiber formation is completed by the third trimester of development in most mammalian species In birds, individual embryonic myoblasts are committed before fusion to forming slow, fast, or mixed primary fibers Avian secondary fibers may also be slow, fast, or mixed Satellite cells, which represent approximately 30% of muscle nuclei in neonates and approximately 4% in adults, not express fiber-type characteristics until fusion with a myofiber Postnatal muscle has a limited capacity to generate new fibers from satellite cells after injury, although a few new fibers may form one to two months after birth MYOFIBRILLOGENESIS MYOGENESIS Myogenesis involves three populations of precursor cells, embryonic and fetal myoblasts and postnatal satellite cells, that appear sequentially during development (Fig 1) Embryonic myoblasts undergo extensive proliferation at the presumptive location of muscles, and then fuse into primary myofibers Fetal myoblasts form secondary fibers and add nuclei to growing primary myofibers Satellite cells lie beneath the basal lamina of myofibers, contribute DNA to growing myofibers, and serve as a precursor pool for muscle repair following injury 688 Contractile myofibrils within myofibers extend the length of the myofiber and are composed of overlapping thick and thin filaments organized into repeating units called sarcomeres Each sarcomere is bounded by perpendicular z-lines, which organize thin filaments and attach, via titin, to the thick filaments Z-lines extend across the muscle cell and attach by transmembrane structures to the extracellular connective tissue Sarcomeres, which are about 2.6-mM long at rest, also serve as scaffolds for the sarcoplasmic reticulum, mitochondria, and metabolic enzymes Myofibrillogenesis begins with aggregation of repeating units of thin filament (actin) and z-line proteins Encyclopedia of Animal Science DOI: 10.1081/E EAS 120019740 Copyright D 2005 by Marcel Dekker, Inc All rights reserved Ontogeny: Muscle 689 many possible combinations of characteristics but fiber type is most simply described as red (slow, oxidative, type I), intermediate (fast, oxidative and glycolytic, type IIa), or white (fast, glycolytic, type IIb) Most muscle proteins have fiber-type specific isoforms Fiber-type characteristics are developmentally determined but may be modulated by subsequent neural, endocrine, and mechanical influences Myosin heavy chain (MHC), an abundant fiber-type marker, undergoes a developmental transition from embryonic to neonatal to adult isoforms Expression of different proteins with fiber-type specific isoforms is weakly coordinated in transitional fibers In the embryo, slow primary fibers are larger than secondary fibers, but fast fibers become larger after birth MUSCLE HYPERTROPHY Fig Formation of myofibers during development Myogenic determination results in three pools of precursor cells: embryonic myoblasts, fetal myoblasts and satellite cells Myoblasts fuse into myotubes Synthesis of contractile proteins and organiza tion of sarcomeres result in maturation into myofibers, which have a striated appearance under the microscope Embryonic myoblasts form myofibers with slower contraction speeds and primarily aerobic metabolism Fetal myoblasts organize adjacent to primary fibers and may form slow myofibers or myofibers with faster contraction and primarily anaerobic metabolism Satellite cells proliferate; one of the daughter cells fusing with a myofiber to add myonuclei during postnatal hypertrophy or repair (# Copyright 2003 by J Novakofski.) ( a-actinin) beneath the sarcolemma of myotubes Titin and then myosin are added as the nascent myofibrils migrate away from the sarcolemma and organize into sarcomeres As muscle cells increase in length, new sarcomeres are added at the end of myofibrils FIBER TYPES Myofiber type is defined by a combination of metabolic, contractile, and morphological characteristics There are The postnatal increase in myofiber size requires satellite cell fusion, DNA addition, and a protein synthesis rate greater than the rate of degradation Newly formed myotubes are 10 mm in diameter, growing into 25 100 mm myofibers a several hundredfold increase in mass Insulin-like growth factor-I (IGF-I) is the major factor stimulating hypertrophy IGF-I activates a number of signaling pathways including the calcineurin pathway and the phosphotidylinositiol-3 kinase pathway that increases protein synthesis The proteasome pathway degrades most muscle proteins MESODERM ORIGINS Skeletal muscles of the head, back, abdomen, and limbs have different lineages in the embryo (Fig 2) Muscles of the head originate directly from myoblasts of the cranial mesoderm Myoblasts that form the muscles of the limbs and trunk originate in somites Somites result from segmentation of the paraxial mesoderm along the neural tube and notochord The dorsal portion of the somite forms the dermomyotome, whereas the ventral portion forms the sclerotome, which is subsequently induced to form axial skeleton The dermomyotome then segments into an inner myotome layer and outer dermatome layer Axial muscles (i.e., longissimus, psoas) derive from the dorsomedial or epaxial portion of the myotome, whereas abdominal muscles derive from the ventrolateral or hypaxial portion of the myotome Limb muscles derive from precursors that migrate out of the ventrolateral myotome Anterior somites develop before posterior somites so there is a temporal gradient in myoblast migration, and forelimbs develop before hindlimbs After 690 Ontogeny: Muscle Fig Origin of muscles in the embryo Muscles of the head, back, abdomen, and limbs arise from different developmental lineages, which are established early in embryonic development Shaded areas in the drawing of the embryo give rise to muscles in the corresponding shaded locations of the mature animal Muscles of the head and extraocular muscles originate from the cranial mesoderm, whereas muscles of the body and limbs derive from the myotomes on either side of the neural tube Epaxial muscles develop from the dorsomedial portion of the myotome, whereas hypaxial muscles develop from the ventrolateral portion of the myotome Myoblasts that form limb muscles delaminate from the ventrolateral myotome, migrate into the limbs, and undergo extensive proliferation before fusing into myofibers Organization into individual muscles is directed by hox gene expression and signals from nearby mesoderm that will form connective tissue (# Copyright 2003 by J Novakofski.) migration, myoblasts proliferate extensively at the location of presumptive muscles and aggregate into ventral and dorsal masses before individual muscles form Positional clues for myoblast migration and subsequent formation of individual muscles within limbs are provided by hox gene expression and cartilage derived from the limb bud mesenchyme MYOGENIC DETERMINATION FACTORS Formation of myofibers from mesenchymal precursors is controlled by growth factors that induce or inhibit Fig Myogenesis and myogenic regulation Each step leading to myofiber formation is controlled by growth factors that induce or inhibit myogenesis Activators indicated by an arrow ( ! ), inhibitors indicated by a bar (j ) Wnt, sonic hedge hog (Shh) and bone morphogenic proteins (BMP) are secreted from the neural tube, notochord and lateral ectoderm These secreted growth factors induce expression of myogenic regulatory transcription factors (Pax3, Myf5 and MyoD) in somatic or axial mesoderm Subsequently, proliferation of myoblasts is regulated by insulin like growth factor (IGF I) and fibroblast growth factor (FGF) IGF I and integrin (a cell adhesion protein) induce expression of myogenic transcription factors, MRF4, and myogenin, essential for myoblast fusion IGF I is unique because it stimulates both myoblast proliferation and differen tiation Myostatin is a potent inhibitor of myoblast proliferation and myostatin inactivation results in the increased myofiber of double muscled cattle The proinflammatory cytokine tumor necrosis factor a (TNFa) inhibits myoblast proliferation, fusion, and synthesis of muscle specific proteins, resulting in smaller muscles (# Copyright 2003 by J Novakofski.) Ontogeny: Muscle myogenic regulatory transcription factors (MRFs) mediating the steps in myogenesis (Fig 3) Determination of somitic mesoderm cells into myoblasts begins with induction of Myf5 and MyoD in Pax-3 positive cells of the somite by growth factors from the neural tube, notochord, and ectoderm Although there is functional overlap, Myf5 primarily determines epaxial and MyoD determines hypaxial myoblasts Subsequent expression of MRF4 and myogenin in determined myoblasts mediates differentiation and fusion into myofibers MyoD and myogenin remain expressed at lower levels in mature myofibers Myoblast proliferation and differentiation are mutually exclusive events so myofiber formation can be increased either by stimulating myoblast proliferation or by inhibiting myoblast differentiation Proliferation stops before fusion because elevated MRFs inhibit cell cycle proteins including cyclin-dependent kinases (CDKs), pRB, and p21 Conversely, in proliferating myoblasts, MRF activity is suppressed by Id protein or CDK phosphorylation Satellite cell function depends on expression of the Pax7 transcription factor, which is closely related to the Pax3 essential for myogenic determination and myoblast migration Myf5 and MyoD are upregulated in proliferating satellite cells, whereas myogenin and MRF4 are not expressed until differentiation and fusion Satellite cell divisions are asymmetric with fusion of one daughter cell to a myofiber while the other remains an unfused satellite cell Asymmetry results in the segregation of Numb and differential upregulation of Pax7 and MRFs 691 CONCLUSION Major events in the ontogeny of muscle characteristics occur during embryonic and fetal development, although the bulk of muscle mass is deposited during postnatal growth Muscles in different anatomic locations derive from different embryonic lineages These differences are reflected in the myofiber number and mass of mature muscles and in the specific patterns of metabolic and contractile properties of the myofibers Future insight into these complex processes will enable improvement in livestock production and achievement of biomedical goals such as replacement of diseased or damaged muscles REFERENCES Buckingham, M.; Bajard, L.; Chang, T.; Daubas, P.; Hadchouel, J.; Meilhac, S.; Montarras, D.; Rocancourt, D.; Relaix, F The formation of skeletal muscle: from somite to limb J Anat 2003, 202 (15), 59 68 Novakofski, J.; McCusker, R Skeletal and Muscular Systems In Biology of the Pig, 2nd Ed.; Pond, W.G., Mesmann, H.J., Eds.; Cornell University Press: Ithaca, 2001; 454 502 Chap Stem Cells and Cell Signaling in Skeletal Myogenesis; Sassoon, D.A., Ed.; Advances in Developmental Biology and Biochemistry; Elsevier: New York, 2002; Vol 11 Wigmore, P.M.; Evans, D.J Molecular and cellular mechanisms involved in the generation of fiber diversity during myogenesis Int Rev Cytol 2002, 216, 175 232 Ontogeny: Skeleton A M Oberbauer K D Evans University of California, Davis, California, U.S.A INTRODUCTION Bone is a ‘‘specialized form of connective tissue.’’ The role of the skeleton is twofold: structural support and calcium homeostasis In addition to bone, cartilage is an essential component in skeletal function Cartilage serves as a precursor of endochondral bone formation and minimizes friction at bone joints Bone is composed of an organic matrix of collagen and proteoglycans (osteoid) embedded with hydroxyapatite crystals containing calcium and phosphorus salts The osteoid matrix is primarily type I collagen, whereas in cartilage tissue, the predominant component is type II collagen TISSUE ORIGIN Four cell types in bone (osteoblasts, osteocytes, bone lining cells, and osteoclasts) and three in cartilage (chondroblasts, chondrocytes, and chondroclasts) are responsible for the synthesis and maintenance of bone and cartilage matrix The osteoclasts and chondroclasts are of hemopoietic stem cell origin, whereas the remaining cell types differentiate from mesenchymal stem cells experiencing different local environmental inputs (e.g., oxygen tension or extracellular hormonal signaling) EMBRYONIC FORMATION Bone, the skeletal organ, is classified as being either intramembranous or endochondral in origin Intramembranous bone is formed by the in situ differentiation of mesenchymal progenitor cells into osteoblasts that secrete osteoid; this matrix then undergoes calcification with hydroxyapatite crystal deposition.[1] In contrast, endochondral bones are embryonically formed as a cartilage anlage Mesenchymal progenitor cells differentiate into chondroblasts and mature to chondrocytes that coalesce into a model representing a miniature version of the future bone Chondrocytes proliferate and then mature, a process that includes hypertrophy with secretion and mineralization of matrix Through this maturation process, the local milieu changes, inducing the death of the most centrally 692 located chondrocytes, thereby permitting blood vessel invasion through the nutrient foramen (Fig 1) Accompanying the vasculature are marrow stem cells, osteoblast progenitor cells, and osteoclast and chondroclast precursors Chondroclasts locally degrade mineralized cartilage matrix, whereas osteoblasts utilize the cartilage matrix remnants as a substrate for osteoid deposition This central invasion forms the primary center of ossification At each of the two ends of the anlage, the vascular invasion is reiterated, generating three distinct centers of ossification: the primary and two secondary centers The ossification centers remain distinct due to a retained cartilage disk between the primary and each secondary center The cartilage disk, or growth plate, offers growth potential (discussed later in this article) Additional cartilage remains at the extreme ends of the anlage to become the articular cartilage essential in joint function The bone is now defined into anatomical regions relative to the growth plates The central region enveloping the primary center of ossification is the diaphysis The regions encompassing the growth plate are the metaphyses, whereas the two ends of the bone are the epiphyses.[2] GROWTH PLATE Chondrocytes within the growth plate are organized in a precise pattern reflecting cell functionality Randomly distributed stem cell chondrocytes lie adjacent to the epiphysis in a region termed the resting zone Resting zone cells induced to divide produce columns of clonally expanding cells, forming the proliferative zone The proliferative zone chondrocytes then mature in their metabolic activities, secrete additional matrix, and hypertrophy This expansive proliferation and hypertrophy occurring in both growth plates essentially pushes the ends of the bone apart, resulting in overall elongation The retention of cartilaginous growth plates permits elongation of bone by an internal mechanism, enabling structural support and maintenance of the physical configuration of the bone necessary for tendon and ligament insertion sites In contrast to the endochondral growth process, intramembranous bone enlarges by appositional deposition of osteoid matrix Encyclopedia of Animal Science DOI: 10.1081/E EAS 120019742 Copyright D 2005 by Marcel Dekker, Inc All rights reserved Ontogeny: Skeleton 693 Fig Endochondral ossification stages (Reprinted from Fig 3.39, 37th edition of Gray’s Anatomy, 1989, with permission from Elsevier.) CELL TYPES The osteoblast, the primary bone-forming cell, secretes type I collagen and proteoglycans to form a nonmineralized matrix that serves as scaffolding for hydroxyapatite crystal deposition by osteoblasts.[3] The osteoblast requires a surface to lay down the osteoid As the osteoblast becomes surrounded by mineralized matrix, it changes phenotype by losing much of its protein production organelles and forming protoplasmic processes that connect via gap junctions to the adjacent protoplasmic processes of other encased osteoblasts.[4] Once surrounded by matrix, the cell is designated an osteocyte The bulk of the osteocyte occupies a space within the bone known as the lacuna, while the protoplasmic processes occupy spaces termed canaliculi.[3] The protoplasmic process connections between osteocytes allow cellular communication, which becomes important during times of increased mechanical stress and hormonal control of serum calcium levels In contrast to the osteoblast and osteocyte found in areas of active bone formation, bonelining cells are present only on bone surfaces not actively forming bone Bone-lining cells are reserve cells that differentiate into osteoblasts when needed, as during fracture repair, to actively create bone.[3] The osteoclast is the major bone resorbing cell The osteoclast secretes acid hydrolases to dissolve the hydroxyapatite and enzymes to dissolve the protein scaffolding within bone.[5] The osteoclast maintains a polarity with only the side in contact with bone forming a ruffled membrane (Fig 2) This ruffled edge localizes acids and enzymes permitting bone resorption within discrete sites BONE ELONGATION, APPOSITION, ENLARGEMENT Bone undergoes growth in two ways Growth in the longitudinal plane of long bones is achieved through the process of chondrocyte activity within growth plates (endochondral ossification) Widening of long bones and increased size of flat bones is achieved through a process of cell division and subsequent ossification in all directions (appositional growth).[4] Within long bones, appositional growth occurs at the periosteum accompanied by resorption at the endosteum in order for the cortical bone width at the diaphysis to maintain mechanical stability.[4] During the process of endochondral ossification, chondrocytes proliferate, hypertrophy, and mineralize The mineralized cartilage cores produced at the metaphysis of the bone are resorbed by osteoclasts and used as scaffolding on which osteoblasts can begin building bone As the bone lengthens, mechanical forces applied by gravity and surrounding musculature force the bone to reshape itself by resorbing the outer edges of the Fig Activation and communication between the osteoclast and the osteoblast: the BMU 694 Fig Hormonal cascades involved in growth plate pro liferation metaphysis This process ensures that the bone retains the greatest mechanical stability in the face of normal wear and tear.[4] The process of growth plate chondrocyte proliferation, hypertrophy, and mineralization is finely controlled through hormones that act both systemically and locally These hormones include growth hormone (GH), insulinlike growth factor-I (IGF-I), thyroid hormone (T3), estrogen (E2), testosterone, vitamin D (Vit D3), and glucocorticoids (GCs);[6–9] the major effectors are GH and IGF-I Growth hormone acts directly on chondrocytes to induce cell division in the resting zone and stimulates local IGF-I production by the proliferating and hypertrophic cells (Fig 3) Growth hormone also stimulates systemic IGF-I production by the liver Both local and systemic IGF-I promote proliferation and hypertrophy of cells within the growth plate Estrogen (E2) directly drives chondrocyte proliferation and influences the growth plate by increasing GH release from the pituitary Conversely, GCs inhibit GH release by the pituitary Testosterone appears to promote growth plate closure by terminating chondrocyte proliferation after puberty.[8] Likewise, T3 acts directly on the chondrocytes to stop proliferation, although T3 stimulates the pituitary to release GH and promotes IGF-I release from the liver CALCIUM REGULATION One primary function of bone is to serve as a calcium storage depot The resorption of bone for the purpose of replenishing serum calcium levels is hormonally orchestrated Much of the process is regulated by the osteoblast, Ontogeny: Skeleton which signals the osteoclast (Fig 2) The unique relationship between these two cell types is known as the BMU (basic multicellular unit).[10] The major calcium regulating hormones are parathyroid hormone (PTH) and calcitonin, with T3, E2, and cytokines contributing to calcium homeostasis.[6–9,11,12] Low serum calcium levels stimulate PTH release that, along with T3, acts to promote the release of the IL-1 and IL-6 cytokines from osteoblasts These cytokines stimulate bone resorption by the osteoclast leading to calcium release into the fluid surrounding the osteoclast, which is transported into the circulation to replenish serum calcium levels In contrast, E2 inhibits osteoclast resorption by impairing osteoblastic release of these cytokines The other major calcium regulator, calcitonin, is released in response to high serum calcium levels Calcitonin acts directly on the osteoclast to inhibit its resorbing capabilities and promote bone formation through enhancing osteoblast proliferation.[13] MECHANICAL CONTROL Bone constantly undergoes a process, termed remodeling Bone is continuously resorbed by osteoclasts and replaced by osteoblasts daily Much of the remodeling process is regulated by the osteoblast signaling the osteoclast (Fig 2) to create the BMU.[14] The process initiates when bone experiences mechanical stress that generates microdamage This mechanical stress ultimately determines the shape and morphology of the bone Alterations in normal mechanical stress are sensed within the fluid of the canaliculi-connecting osteocytes This activates the osteocytes to signal surrounding osteoblasts to recruit osteoclasts to the area The osteoclasts bore through existing bone to the region requiring reinforcement, and together the osteoblast and osteoclast of the BMU repair and reinforce the stressed bone until it is mechanically sound Remodeling periodically replaces old bone and microcracks, thus maintaining the overall structural integrity of the bone CONCLUSION Mature skeletal size is determined by bone elongation Bone length can be enhanced and accelerated by genetic selection for growth rate alterations or hormonal manipulation that also affect muscle deposition Bone length must be balanced with maintaining bone strength Disturbances in bone strength lead to undesirable consequences for human and animal health including excessive bone breakage Overall, the skeleton is one of the most dynamic physiological systems The constant, simultaneous, precise control over bone formation, degradation, growth, Ontogeny: Skeleton 695 and required mineral regulation is imperative to the maintenance of healthy animals REFERENCES Aubin, J.E.; Liu, F The Osteoblast Lineage In Principles of Bone Biology; Bilezikian, J.P., Raisz, L.G., Rodan, G.A., Eds.; Academic Press Inc.: London, 1996; 51 67 Fetter, A.W; Rhinelander, F.W Normal Bone Anatomy In Textbook of Small Animal Orthopaedics; Newton, C.D., Nunamaker, D.M., Eds.; International Veterinary Informa tion Service Ithaca: New York, 1985 Marks, S.C.; Hermey, D.C The Structure and Develop ment of Bone In Principles of Bone Biology; Bilezikian, J.P., Raisz, L.G., Rodan, G.A., Eds.; Academic Press Inc.: London, 1996; 14 Vaughn, J The Physiology of Bone, 3rd Ed.; Clarendon Press: Oxford, 1981; 17 27 Tietelbaum, S.L Bone resorption by osteoclasts Science 2000, 289 (5484), 1504 1508 Ohlsson, C.; Bengtsson, B A.; Isaksson, O.G.P.; Andreassen, T.T.; Slootweg, M.C Growth hormone and bone Endocr Rev 1998, 19 (1), 55 79 Robson, H.; Siebler, T.; Shalet, S.M.; Williams, G.R Interactions between GH, IGF I, glucocorticoids, and 10 11 12 13 14 thyroid hormones during skeletal growth Pediatr Res 2002, 52 (2), 137 147 Siebler, T.; Robson, H.; Shalet, S.M.; Williams, G.R Glucocorticoids, thyroid hormone and growth hormone interactions: Implications for the growth plate Horm Res 2001, 56 (Supplemental 1), 12 Rickard, D.J.; Subramaniam, M.; Spelsberg, T.C Molec ular and cellular mechanisms of estrogen action on the skeleton J Cell Biochem 1999, 32 33 (Supplemental), 123 132 Frost, H.M Tetracycline based histological analysis of bone remodeling Calcif Tissue Res 1969, (3), 211 237 Hayden, J.M.; Mohan, S.; Baylink, D.J The insulin like growth factor system and the coupling of formation to resorption Bone 1995, 17 (Supplemental 2), 93S 98S Rodan, G.A Introduction to bone biology Bone 1992, 13 (Supplemental 1), S3 S6 Farley, J.; Dimai, H.P.; Stilt Coffing, B.; Farley, P.; Pham, T.; Mohan, S Calcitonin increases the concentration of insulin like growth factors in serum free cultures of human osteoblast line cells Calcif Tissue Int 2000, 67, 247 254 Ott, S.M Theoretical and Methodological Approach In Principles of Bone Biology; Bilezikian, J.P., Raisz, L.G., Rodan, G.A., Eds.; Academic Press Inc.: London, 1996; 231 241 Overall Contributions of Domestic Animals to Society Duane E Ullrey Michigan State University, East Lansing, Michigan, U.S.A INTRODUCTION The domestication of plants and animals may be the most important development in the past 13,000 years of human history Although authorities differ in attributing dates to particular events, this domestication was a necessary prelude to the evolution of civilization as we know it Previously, human migrations followed seasonal shifts in wild food supplies Subsequently, settlements appeared near gardens, orchards, and pastures Food production increased, supporting local increases in population and the spread of humans to previously unoccupied geographical regions Increases in the efficiency of food acquisition and storage made possible the development of crafts and trades, since it was no longer necessary for every family to spend time hunting and gathering food Ultimately, the social and political systems that evolved came to govern much of human activity HISTORICAL BACKGROUND Primates of a lineage now identified as human, diverged from the great apes about million years ago.[1] Not until 10,000 to 15,000 years ago was there an example of animal domestication.[2,3] This is purported to be domestication of the dog’s wolflike ancestor during the hunter gatherer period of human cultural development The primary event initiating livestock domestication was the formation of large, relatively stable agricultural societies some 9000 to 10,000 years ago when cultivation of plants began.[2,4,5] Why it took so long is uncertain, but it has been suggested that events in the late Pleistocene may have played an important role.[1] Improved hunting skills may have depleted the supply of available prey Discoveries in the technology of collecting, processing, and storing foods allowed societies with more effective technologies to prevail over others Human populations were growing, and more efficient food production was required to meet increasing needs Further, the end of the Pleistocene (11,000 B.C.) was coincident with the end of the Ice Age, and the climatic circumstances that followed were more favorable for permanent agricultural settlements and the extension of such settlements into other relatively unpopulated areas 696 Beginning in about 8500 B.C., domestication of cattle, sheep, and goats began in the Near East, particularly in the Fertile Crescent, an arc of land from present-day western Syria and southern Turkey, through northeastern Iraq, to Iran.[1,2,5] Domestication of pigs took place about 9000 years ago both in Europe and in Asia.[2] Chickens were domesticated from jungle fowl in Thailand and adjacent regions about 8000 years ago, and remains of domesticated chickens have been found in neolithic sites in China dating to 6000 B.C Llamas and alpacas were domesticated about 6000 years ago in South America.[2] Concurrently, horses were being domesticated for meat and transportation in the Ukraine.[2] Archeological evidence associating humans and silkworms dates back to about 2500 B.C in China Guinea pigs were domesticated about 3000 to 4000 years ago by the indigenous people of Peru for use as food and in religious ceremonies.[2] About 2500 years ago, rabbits were domesticated in southern Europe Wild turkeys, native to North America, were transported to Europe and domesticated there about 500 years ago.[2] Additional animal species, domesticated before the time of Christ, include asses, Bactrian and dromedary camels, honey bees, bantengs, water buffalos, ducks, yaks, cats, geese, and reindeer.[5,6] CONTRIBUTIONS OF ANIMAL DOMESTICATION As plants and animals underwent domestication, humans acquired the power to alter their ecosystem in ways that favored their immediate needs The balance of animal life was modified either by domestication and directed evolution or by discouraging the presence of wild animals that preyed on crops and herds Arable areas were extended by deforestation and irrigation Increased local production of food encouraged population growth and the formation of stable settlements Archaeological evidence indicates that, at first, a substantial portion of animal food still came from wild animals, but hunting pressure and increasingly intensive agriculture gradually diminished local wild animal populations The association of humans with wild animals was long-standing and undoubtedly led to identification of Encyclopedia of Animal Science DOI: 10.1081/E EAS 120019743 Copyright D 2005 by Marcel Dekker, Inc All rights reserved Overall Contributions of Domestic Animals to Society species that were amenable to domestication A herding instinct and a proclivity for imprinting on humans may have been important The discovery of hoof prints of goats and sheep in the clay of a prehistoric inhabited village (Ganj-Dareh) that flourished around 7000 B.C in the mountains of present-day western Iran provided evidence that no longer were these humans dependent on wild animals for meat.[5] Through conscious or unconscious selection, the anatomy, behavior, and productivity of these sheep and goats were modified Not only did they provide meat and hides, as did their wild relatives, but selection for production of wool or milk added further to their societal value Comparable changes occurred in horses and water buffalo as they were domesticated They could not only be used for meat or milk, but could also be ridden or harnessed to ploughs and other devices that eased the physical burdens of soil preparation, planting, and harvest Horse-mounted cavalrymen proved particularly intimidating in battle There are notable differences between geographical regions in the domesticated species that are present These differences relate to the wild species that were indigenous to the region, to physiologic tolerance of the environment by their domestic counterparts, and in some regions, to religious traditions governing acceptability of particular species as food Although there are cultural differences within and between countries in the uses of animals, their domestication enriched human society by providing companionship, recreation, materials needed for clothing, readily available food, and power to assist in laborintensive tasks Much of modern medical technology was derived through research with dogs, pigs, calves, and sheep Porcine cardiac tissue has been used to replace failing valves in the human heart, and researchers now study transgenic pigs as potential organ donors for humans with terminal organ dysfunction.[7] Unfortunately, the increasing density of human populations also has been associated with the advent of epidemic diseases, some of 697 which had their origins in, or were spread by, domestic animals.[1] CONCLUSIONS Domestic animals have played an integral role in the formation of modern human society Before animal domestication, humans led a relatively nomadic existence in their search for food, absent the social and political organizations that govern current community affairs Relief from the relentless search for food and the increased efficiency with which it was produced in stable settlements allowed for development of the trades, cultural arts, medical advances, and the various disciplines of science that now so enrich our lives REFERENCES Diamond, J Evolution, consequences and future of plant and animal domestication Nature 2002, 418, 700 707 Price, E.O Animal Domestication and Behavior; CABI Publishing: New York, 2002 Clutton Brock, J Origins of the Dog: Domestication and Early History In The Domestic Dog: Its Evolution, Behavior and Interactions with People; Cambridge Univer sity Press: Cambridge, UK, 1995; 20 Harlan, J.R The Living Fields: Our Agricultural Heritage; Cambridge University Press: New York, 1995 Clutton Brock, J A Natural History of Domesticated Mammals, 2nd Ed.; Cambridge University Press: Cam bridge, UK, 1999 Leonard, J.N The Emergence of Man: The First Farmers; Time Life Books: New York, 1973 Ullrey, D.E.; Bernard, J Other Animals, Other Uses, Other Opportunities In Introduction to Animal Science; Pond, W.G., Pond, K.R, Eds.; John Wiley & Sons, Inc.: New York, 2000; 553 583  ... are formed from fusion of mononucleated myoblasts into myotubes Subsequent synthesis of contractile myofibrils and organization into sarcomeres within myotubes result in maturation into myofibers... Mode of accretion or expansion Molecular and ultrastructural markers Late fetal tissue and adipocyte morphology Neonatal Tissue and adipocyte morphology Mode of accretion or expansion Accretion... side of the neural tube Epaxial muscles develop from the dorsomedial portion of the myotome, whereas hypaxial muscles develop from the ventrolateral portion of the myotome Myoblasts that form