Cell Differentiation and Embryonic Development BIO101 - Bora Zivkovic - Lecture 2 - Part 2 There are about 210 types of human cells, e.g., nerve cells, muscle cells, skin cells, blood cells, etc. Wikipedia has a nice comprehensive listing of all the types of human cells. What makes one cell type different from the other cell types? After all, each cell in the body has exactly the same genome (the entire DNA sequence). How do different cells grow to look so different and to perform such different functions? And how do they get to be that way, out of homogenous (single cell type) early embryonic cells that are produced by cell division of the zygote (the fertilized egg)? The difference between cell types is in the pattern of gene expression, i.e., which genes are turned on and which genes are turned off. Genes that code for enzymes involved in detoxification are transribed in lver cells, but there is not need for them to be expressed in muscle cells or neurons. Genes that code for proteins that are involved in muscle contraction need not be transcribed in white blood cells. The patterns of gene expression are specific to cell types and are directly resposible for the differences between morphologies and functions of different cells. How do different cell types decide which genes to turn on or off? This is the result of processes occuring during embryonic development. The zygote (fertilized egg) appears to be a sphere. It may look homogenous, i.e., with no up and down, left or right. However, this is not so. The point of entry of the sperm cell into the egg may provide polarity for the cell in some organisms. In others, mother may deposit mRNAs or proteins in one particular part of the egg cell. In yet others, the immediate environment of the egg (e.g., the uterine lining, or the surface of the soil) may define polarity of the cell. When the zygote divides, first into 2, then 4, 8, 16 and more cells, some of those daughter cells are on one pole (e.g., containing maternal chemicals) and the others on the other pole (e.g., not containing maternal chemicals). Presence of chemicals (or other influences) starts altering the decisions as to which genes will be turned on or off. As some of the genes in some of the cells turn on, they may code for proteins that slowly diffuse through the developing early embryo. Low, medium and high concentrations of those chemicals are found in diferent areas of the embryo depending on the distance from the cell that produces that chemical. Other cells respond to the concentration of that chemical by turning particular genes on or off (in a manner similar to the effects of steroid hormones acting via nuclear receptors, described last week). Thus the position (location) of a cell in the early embryo largely determines what cell type it will become in the end of the process of the embryonic development. The process of altering the pattern of gene expression and thus becoming a cell of a particular type is called cell differentiation. The zygote is a totipotent cell - its daughter cells can become any cell type. As the development proceeds, some of the cells become pluripotent - they can become many, but not all cell types. Later on, the specificity narrows down further and a particular stem cell can turn into only a very limited number of cell types, e.g., a few types of blood cells, but not bone or brain cells or anything else. That is why embryonic stem cell research is much more promising than the adult stem cell research. The mechanism by which diffusible chemicals synthesized by one embryonic cell induces differentiation of other cells in the embryo is called induction. Turning genes on Fertilization and Early Embryonic Development Fertilization and Early Embryonic Development Bởi: OpenStaxCollege The process in which an organism develops from a single-celled zygote to a multicellular organism is complex and well-regulated The early stages of embryonic development are also crucial for ensuring the fitness of the organism Fertilization Fertilization, pictured in [link]a is the process in which gametes (an egg and sperm) fuse to form a zygote The egg and sperm each contain one set of chromosomes To ensure that the offspring has only one complete diploid set of chromosomes, only one sperm must fuse with one egg In mammals, the egg is protected by a layer of extracellular matrix consisting mainly of glycoproteins called the zona pellucida When a sperm binds to the zona pellucida, a series of biochemical events, called the acrosomal reactions, take place In placental mammals, the acrosome contains digestive enzymes that initiate the degradation of the glycoprotein matrix protecting the egg and allowing the sperm plasma membrane to fuse with the egg plasma membrane, as illustrated in [link]b The fusion of these two membranes creates an opening through which the sperm nucleus is transferred into the ovum The nuclear membranes of the egg and sperm break down and the two haploid genomes condense to form a diploid genome (a) Fertilization is the process in which sperm and egg fuse to form a zygote (b) Acrosomal reactions help the sperm degrade the glycoprotein matrix protecting the egg and allow the sperm 1/7 Fertilization and Early Embryonic Development to transfer its nucleus (credit: (b) modification of work by Mariana Ruiz Villareal; scale-bar data from Matt Russell) To ensure that no more than one sperm fertilizes the egg, once the acrosomal reactions take place at one location of the egg membrane, the egg releases proteins in other locations to prevent other sperm from fusing with the egg If this mechanism fails, multiple sperm can fuse with the egg, resulting in polyspermy The resulting embryo is not genetically viable and dies within a few days Cleavage and Blastula Stage The development of multi-cellular organisms begins from a single-celled zygote, which undergoes rapid cell division to form the blastula The rapid, multiple rounds of cell division are termed cleavage Cleavage is illustrated in ([link]a) After the cleavage has produced over 100 cells, the embryo is called a blastula The blastula is usually a spherical layer of cells (the blastoderm) surrounding a fluid-filled or yolk-filled cavity (the blastocoel) Mammals at this stage form a structure called the blastocyst, characterized by an inner cell mass that is distinct from the surrounding blastula, shown in [link]b During cleavage, the cells divide without an increase in mass; that is, one large single-celled zygote divides into multiple smaller cells Each cell within the blastula is called a blastomere (a) During cleavage, the zygote rapidly divides into multiple cells without increasing in size (b) The cells rearrange themselves to form a hollow ball with a fluid-filled or yolk-filled cavity called the blastula (credit a: modification of work by Gray’s Anatomy; credit b: modification of work by Pearson Scott Foresman, donated to the Wikimedia Foundation) Cleavage can take place in two ways: holoblastic (total) cleavage or meroblastic (partial) cleavage The type of cleavage depends on the amount of yolk in the eggs In placental mammals (including humans) where nourishment is provided by the mother’s body, the eggs have a very small amount of yolk and undergo holoblastic cleavage Other species, 2/7 Fertilization and Early Embryonic Development such as birds, with a lot of yolk in the egg to nourish the embryo during development, undergo meroblastic cleavage In mammals, the blastula forms the blastocyst in the next stage of development Here the cells in the blastula arrange themselves in two layers: the inner cell mass, and an outer layer called the trophoblast The inner cell mass is also known as the embryoblast and this mass of cells will go on to form the embryo At this stage of development, illustrated in [link] the inner cell mass consists of embryonic stem cells that will differentiate into the different cell types needed by the organism The trophoblast will contribute to the placenta and nourish the embryo The rearrangement of the cells in the mammalian blastula to two layers—the inner cell mass and the trophoblast—results in the formation of the blastocyst Link to Learning Visit the Virtual Human Embryo project at the Endowment for Human Development site to step through an interactive that shows the stages of embryo development, including micrographs and rotating 3-D images Gastrulation The typical blastula is a ball of cells The next stage in embryonic development is the formation of the body plan The cells in the blastula rearrange themselves spatially to form three layers of cells This process is called gastrulation ...Early Childhood Development and Disability: A discussion paper Early Childhood Development and Disability: A discussion paper WHO Library Cataloguing-in-Publication Data Early childhood development and disability: discussion paper. 1.Child development. 2.Disabled children 3.Child welfare. 4.Child health services. I.World Health Organization. II.UNICEF. ISBN 978 92 4 150406 5 NLM classication: WS 368) © World Health Organization 2012 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@who.int). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/ copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specic companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. Editing: Donna Phillips Cover photo: CBM/argum/Einberger (taken in Tanzania) Design and layout: Inís Communication – www.iniscommunication.com Printed in: Malta Early Childhood Development and Disability 3 Contents 1. Introduction 5 2. Children with disabilities 7 What is disability and who are children with disabilities? 7 How many children with disabilities are there? 8 What are the rights of children with disabilities? 8 3. Early childhood development and disability 11 What factors aect child development? 13 Why support the development of children with disabilities? 18 4. How can we support the development of children with disabilities? 21 Early identication of development delays and/or disabilities 22 Assessment and planning for early intervention 22 Service provision 23 5. Conclusion and next steps: Implications for policy and programming 31 References 34 Early Childhood Development and Disability 4 Centre for Disability in Development/ Shumon Ahmed(taken in Bangladesh) Introduction 5 1. Introduction Early childhood is the period from prenatal development to eight years of age. It is a crucial phase of growth and development because experiences during early childhood can inuence outcomes across the entire course of an individual’s life (1,2). For all children, early childhood provides an important window of opportunity to prepare the foundation for life-long learning and participation, while preventing potential delays in Polypyrimidine tract-binding protein is essential for early mouse development and embryonic stem cell proliferation Masaki Shibayama*, Satona Ohno*, Takashi Osaka, Reiko Sakamoto, Akinori Tokunaga, Yuhki Nakatake, Mitsuharu Sato and Nobuaki Yoshida Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Japan Introduction Mouse embryonic stem (ES) cells are established from the inner cell mass (ICM) of blastocysts. ES cells are defined by their ability to give rise to a variety of mature progeny while maintaining their capacity to self-renew. Self-renewal is the process by which a stem cell divides to generate one or two daughter stem cells with developmental potentials that are indistinguish- able from that of the mother cell. This process is cen- tral to development, as well as to the maintenance of adult tissues in complex and long-lived organisms. Self-renewal of ES cells is coordinated by multiple pathways, some of which are conserved among diverse types of stem cells, but others of which are restricted to certain cell types or tissues [1]. In some of these pathways, alternatively spliced gene products have a variety of functions across multiple developmental stages [2]. In addition, computational and experimental analyses have suggested that alternative splicing is important for ES cell self-renewal and differentiation [3]. However, the mechanisms by which molecules that Keywords cell cycle; embryonic stem cells; knockout mouse; polypyrimidine tract-binding protein; proliferation Correspondence N. Yoshida, Laboratory of Developmental Genetics, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan Fax: +81 3 5449 5455 Tel: +81 3 5449 5753 E-mail: nobuaki@ims.u-tokyo.ac.jp *These authors contributed equally to this work (Received 15 July 2009, revised 11 September 2009, accepted 15 September 2009) doi:10.1111/j.1742-4658.2009.07380.x Polypyrimidine tract-binding protein (PTB) is a widely expressed RNA- binding protein with multiple roles in RNA processing, including the splic- ing of alternative exons, mRNA stability, mRNA localization, and internal ribosome entry site-dependent translation. Although it has been reported that increased expression of PTB is correlated with cancer cell growth, the role of PTB in mammalian development is still unclear. Here, we report that a homozygous mutation in the mouse Ptb gene causes embryonic lethality shortly after implantation. We also established Ptb ) ⁄ ) embryonic stem (ES) cell lines and found that these mutant cells exhibited severe defects in cell proliferation without aberrant differentiation in vitro or in vivo. Furthermore, cell cycle analysis and a cell synchronization assay revealed that Ptb ) ⁄ ) ES cells have a prolonged G 2 ⁄ M phase. Thus, our data indicate that PTB is essential for early mouse development and ES cell proliferation. Abbreviations AP, alkaline phosphatase; E, embryonic day; EB, embryoid body; ES, embryonic stem; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ICM, inner cell mass; IRES, internal ribosome entry site; LIF, leukemia inhibitory factor; PI, propidium iodide; PTB, polypyrimidine tract-binding protein; SCID, severe combined immunodeficiency; SD, standard deviation; SSEA-1, stage-specific embryonic antigen-1. 6658 FEBS Journal 276 (2009) 6658–6668 ª 2009 The Authors Journal compilation ª 2009 FEBS regulate alternative splicing contribute to In vitro embryonic developmental phosphorylation of the cellular nucleic acid binding protein by cAMP-dependent protein kinase, and its relevance for biochemical activities Vero ´ nica A. Lombardo, Pablo Armas, Andrea M. J. Weiner and Nora B. Calcaterra Divisio ´ n Biologı ´ a del Desarrollo, IBR – CONICET, Area Biologı ´ a General, Facultad de Ciencias Bioquı ´ micas y Farmace ´ uticas, Universidad Nacional de Rosario, Argentina The zinc-finger cellular nucleic acid binding protein (CNBP) shows striking sequence conservation among vertebrates [1]. Recent works show that CNBP is required for forebrain formation during vertebrate organogenesis. Cnbp-null mutant mice are embryonic lethal and show severe forebrain truncation and facial abnormalities due to a lack of proper morphogenetic movements of the anterior visceral endoderm during Keywords CNBP; Danio rerio; embryogenesis; phosphorylation; PKA Correspondence N. B. Calcaterra, IBR – CONICET, A ´ rea Biologı ´ a General, Dpto. de Ciencias Biolo ´ gicas, Facultad de Ciencias Bioquı ´ micas y Farmace ´ uticas, Universidad Nacional de Rosario, Suipacha 531 (S2002LRK) Rosario, Argentina Tel ⁄ Fax: +54 341 4804601 E-mail: calcaterra@ibr.gov.ar or ncalcate@fbioyf.unr.edu.ar Database CNBP S158A nucleotide sequence data is available in the GenBank database under the accession number DQ519386 (Received 9 October 2006, revised 6 November 2006, accepted 15 November 2006) doi:10.1111/j.1742-4658.2006.05596.x The zinc-finger cellular nucleic acid binding protein (CNBP) is a strikingly conserved single-stranded nucleic acid binding protein essential for normal forebrain formation during mouse and chick embryogenesis. CNBP cDNAs from a number of vertebrates have been cloned and analysed. CNBP is mainly conformed by seven retroviral Cys-Cys-His-Cys zinc-knuckles and a glycine ⁄ arginine rich region box. CNBP amino acid sequences show a puta- tive Pro-Glu-Ser-Thr site of proteolysis and several putative phosphoryla- tion sites. In this study, we analysed CNBP phosphorylation by embryonic kinases and its consequences on CNBP biochemical activities. We report that CNBP is differentially phosphorylated by Danio rerio embryonic extracts. In vitro CNBP phosphorylation is basal and constant at early embryonic developmental stages, it begins to increase after mid-blastula transition stage reaching the highest level at 48 hours postfertilization stage, and decreases thereafter to basal levels at 5 days postfertilization. The cAMP-dependent protein kinase (PKA) was identified as responsible for phosphorylation on the unique CNBP conserved putative phosphoryla- tion site. Site-directed mutagenesis replacing the PKA phospho-acceptor amino acid residue impairs CNBP phosphorylation, suggesting that phos- phorylation may not only exist in D. rerio but also in other vertebrates. CNBP phosphorylation does not change single-stranded nucleic acid bind- ing capability. Instead, it promotes in vitro the annealing of complementary oligonucleotides representing the CT element (CCCTCCCC) from the human cellular myelocytomatosis oncogene (c-myc) promoter, an element responsible for c-myc enhancer transcription. Our results suggest that phos- phorylation might be a conserved post-translational modification that allows CNBP to perform a fine tune expression regulation of a group of target genes, including c-myc, during vertebrate embryogenesis. Abbreviations CCHC, BioMed Central Page 1 of 5 (page number not for citation purposes) Head & Face Medicine Open Access Research The role of apoptosis in early embryonic development of the adenohypophysis in rats Jens Weingärtner 1 , Kristina Lotz 2 , Andreas Faltermeier 3 , Oliver Driemel 4 , Johannes Kleinheinz* 5 , Tomas Gedrange 6 and Peter Proff 3 Address: 1 Department of Anatomy and Cell Biology, Ernst Moritz Arndt University Greifswald, Friedrich Löffler Straße 23c, D-17487 Greifswald, Germany, 2 Department of Gynecology and Obstetrics, Ernst Moritz Arndt University Greifswald, Wollweberstr. 1, D-17487 Greifswald, Germany, 3 Department of Orthodontics, University of Regensburg, F.J. Strauss-Allee 11, D-93042 Regensburg, Germany, 4 Department of Oral and Maxillofacial Surgery, University of Regensburg, F.J. Strauss-Allee 11, D-93042 Regensburg, Germany, 5 Department of Oral and Maxillofacial Surgery, University of Münster, Waldeyerstraße 30, D-48129 Münster, Germany and 6 Department of Orthodontics, Preventive and Pediatric Dentistry, Ernst Moritz Arndt University Greifswald, Rotgerberstr. 8, D-17489 Greifswald, Germany Email: Jens Weingärtner - weingaer@uni-greifswald.de; Kristina Lotz - lotz@uni-greifswald.de; Andreas Faltermeier - andreas.faltermeier@klinik.uni-regensburg.de; Oliver Driemel - oliver.driemel@klinik.uni-regensburg.de; Johannes Kleinheinz* - Johannes.Kleinheinz@ukmuenster.de; Tomas Gedrange - gedrange@web.de; Peter Proff - p.c.proff@gmx.net * Corresponding author Abstract Background: Apoptosis is involved in fundamental processes of life, like embryonic development, tissue homeostasis, or immune defense. Defects in apoptosis cause or contribute to developmental malformation, cancer, and degenerative disorders. Methods: The developing adenohypophysis area of rat fetuses was studied at the embryonic stage 13.5 (gestational day) for apoptotic and proliferative cell activities using histological serial sections. Results: A high cell proliferation rate was observed throughout the adenohypophysis. In contrast, apoptotic cells visualized by evidence of active caspase-3, were detected only in the basal epithelial cones as an introducing event for fusion and closure of the pharyngeal roof. Conclusion: We can clearly show an increasing number of apoptotic events only at the basic fusion sides of the adenohypophysis as well as in the opening region of this organ. Apoptotic destruction of epithelial cells at the basal cones of the adenohypophysis begins even before differentiation of the adenohypophyseal cells and their contact with the neurohypophysis. In early stages of development, thus, apoptotic activity of the adenohypophysis is restricted to the basal areas mentioned. In our test animals, the adenohypophysis develops after closure of the anterior neuroporus. Background The adenohypophysis (Rathke pouch) is derived from the ectoderm and develops during the embryonic stage in the pharyngeal roof in front of the pharyngeal membrane before the anterior neuroporus closes. According to Starck (1975), the primordial Rathke pouch (saccus hypophy- sealis) is a transverse depression in the pharyngeal roof abutting the bottom of the diencephalon without inter- posed mesenchymal cells [1]. Later, the pouch loses con- nection with the pharyngeal roof, while a multitude of Published: 23 July 2008 Head & Face Medicine 2008, 4:13 doi:10.1186/1746-160X-4-13 Received: 16 May 2008 Accepted: 23 July 2008 This article is available from: http://www.head-face-med.com/content/4/1/13 © 2008 Weingärtner et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Head & Face Medicine 2008, 4:13 http://www.head-face-med.com/content/4/1/13 Page 2 of 5 (page number not for citation ... amount of yolk and undergo holoblastic cleavage Other species, 2/7 Fertilization and Early Embryonic Development such as birds, with a lot of yolk in the egg to nourish the embryo during development, ... layer and each germ layer differentiates into different organ systems 3/7 Fertilization and Early Embryonic Development The three germs layers, shown in [link], are the endoderm, the ectoderm, and. .. should be selected and how they 4/7 Fertilization and Early Embryonic Development should be selected are topics of much debate within the worldwide medical community The ethical and moral line is