Embryonic Development

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 Embryonic Development Embryonic Development Bởi: OpenStaxCollege Throughout this chapter, we will express embryonic and fetal ages in terms of weeks from fertilization, commonly called conception The period of time required for full development of a fetus in utero is referred to as gestation (gestare = “to carry” or “to bear”) It can be subdivided into distinct gestational periods The first weeks of prenatal development are referred to as the pre-embryonic stage A developing human is referred to as an embryo during weeks 3–8, and a fetus from the ninth week of gestation until birth In this section, we’ll cover the pre-embryonic and embryonic stages of development, which are characterized by cell division, migration, and differentiation By the end of the embryonic period, all of the organ systems are structured in rudimentary form, although the organs themselves are either nonfunctional or only semi-functional Pre-implantation Embryonic Development Following fertilization, the zygote and its associated membranes, together referred to as the conceptus, continue to be projected toward the uterus by peristalsis and beating cilia During its journey to the uterus, the zygote undergoes five or six rapid mitotic cell divisions Although each cleavage results in more cells, it does not increase the total volume of the conceptus ([link]) Each daughter cell produced by cleavage is called a blastomere (blastos = “germ,” in the sense of a seed or sprout) Approximately days after fertilization, a 16-cell conceptus reaches the uterus The cells that had been loosely grouped are now compacted and look more like a solid mass The name given to this structure is the morula (morula = “little mulberry”) Once inside the uterus, the conceptus floats freely for several more days It continues to divide, creating a ball of approximately 100 cells, and consuming nutritive endometrial secretions called uterine milk while the uterine lining thickens The ball of now tightly bound cells starts to secrete fluid and organize themselves around a fluid-filled cavity, the blastocoel At this developmental stage, the conceptus is referred to as a blastocyst Within this structure, a group of cells forms into an inner cell mass, which is fated to become the embryo The cells that form the outer shell are called trophoblasts (trophe = “to feed” or “to nourish”) These cells will develop into the chorionic sac and the fetal portion of the placenta (the organ of nutrient, waste, and gas exchange between mother and the developing offspring) 1/18 Embryonic Development The inner mass of embryonic cells is totipotent during this stage, meaning that each cell has the potential to differentiate into any cell type in the human body Totipotency lasts for only a few days before the cells’ fates are set as being the precursors to a specific lineage of cells Pre-Embryonic Cleavages Pre-embryonic cleavages make use of the abundant cytoplasm of the conceptus as the cells rapidly divide without changing the total volume As the blastocyst forms, the trophoblast excretes enzymes that begin to degrade the zona pellucida In a process called “hatching,” the conceptus breaks free of the zona pellucida in preparation for implantation View this time-lapse movie of a conceptus starting at day What is the first structure you see? At what point in the movie does the blastocoel first appear? What event occurs at the end of the movie? 2/18 Embryonic Development Implantation At the end of the first week, the blastocyst comes in contact with the uterine wall and adheres to it, embedding itself in the uterine lining via the trophoblast cells Thus begins the process of implantation, which signals the end of the pre-embryonic stage of development ([link]) Implantation can be accompanied by minor bleeding The blastocyst typically implants in the fundus of the uterus or on the posterior wall However, if the endometrium is not fully developed and ready to receive the blastocyst, the blastocyst will detach and find a better spot A significant percentage (50–75 percent) of blastocysts fail to implant; when this occurs, the blastocyst is shed with the endometrium during menses The high rate of implantation failure is one reason why pregnancy typically requires several ovulation cycles to achieve Pre-Embryonic Development Ovulation, fertilization, pre-embryonic development, and implantation occur at specific locations within the female reproductive system in a time span of approximately week When implantation succeeds and the blastocyst adheres to the endometrium, the superficial cells of the trophoblast fuse with each other, forming the syncytiotrophoblast, a multinucleated body that digests endometrial cells to firmly secure the blastocyst to the uterine wall In response, the uterine mucosa rebuilds itself and envelops the blastocyst ([link]) The trophoblast secretes human chorionic gonadotropin (hCG), a 3/18 Embryonic Development hormone that directs the corpus luteum to survive, enlarge, ...BioMed Central Page 1 of 22 (page number not for citation purposes) Reproductive Biology and Endocrinology Open Access Research Peptidylarginine deiminase (PAD) is a mouse cortical granule protein that plays a role in preimplantation embryonic development Min Liu 1 , Andrea Oh 1 , Patricia Calarco 2 , Michiyuki Yamada 3 , Scott A Coonrod 4 and Prue Talbot* 1 Address: 1 Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA, 2 Department of Anatomy and Medicine, School of Medicine, University of California, San Francisco, California 94143, USA, 3 Graduate School of Integrated Science, Yokohama City University, Yokohama, 236-0027 Japan and 4 Weill Medical College of Cornell University, New York, NY 10021, USA Email: Min Liu - corticalgranules@hotmail.com; Andrea Oh - andrea.oh@email.ucr.edu; Patricia Calarco - calarco@itsa.ucsf.edu; Michiyuki Yamada - myamada@yokohama-cu.ac.jp; Scott A Coonrod - scc2003@med.cornell.edu; Prue Talbot* - talbot@ucr.edu * Corresponding author Abstract Background: While mammalian cortical granules are important in fertilization, their biochemical composition and functions are not fully understood. We previously showed that the ABL2 antibody, made against zona free mouse blastocysts, binds to a 75-kDa cortical granule protein (p75) present in a subpopulation of mouse cortical granules. The purpose of this study was to identify and characterize p75, examine its distribution in unfertilized oocytes and preimplantation embryos, and investigate its biological role in fertilization. Results: To identify p75, the protein was immunoprecipitated from ovarian lysates with the ABL2 antibody and analyzed by tandem mass spectrometry (MS/MS). A partial amino acid sequence (VLIGGSFY) was obtained, searched against the NCBI nonredundant database using two independent programs, and matched to mouse peptidylarginine deiminase (PAD). When PAD antibody was used to probe western blots of p75, the antibody detected a single protein band with a molecular weight of 75 kDa, confirming our mass spectrometric identification of p75. Immunohistochemistry demonstrated that PAD was present in the cortical granules of unfertilized oocytes and was released from activated and in vivo fertilized oocytes. After its release, PAD was observed in the perivitelline space, and some PAD remained associated with the oolemma and blastomeres' plasma membranes as a peripheral membrane protein until the blastocyst stage of development. In vitro treatment of 2-cell embryos with the ABL2 antibody or a PAD specific antibody retarded preimplantation development, suggesting that cortical granule PAD plays a role after its release in preimplantation cleavage and early embryonic development. Conclusion: Our data showed that PAD is present in the cortical granules of mouse oocytes, is released extracellularly during the cortical reaction, and remains associated with the blastomeres' surfaces as a peripheral membrane protein until the blastocyst stage of development. Our in vitro study supports the idea that extracellular PAD functions in preimplantation development. Published: 01 September 2005 Reproductive Biology and Endocrinology 2005, 3:42 doi:10.1186/1477-7827-3- 42 Received: 18 July 2005 Accepted: 01 September 2005 This article is available from: http://www.rbej.com/content/3/1/42 © 2005 Liu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative 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, THE FEBS ⁄ EMBO WOMEN IN SCIENCE LECTURE ‘Big frog, small frog’ – maintaining proportions in embryonic development Delivered on 2 July 2008 at the 33 rd FEBS Congress in Athens, Greece Naama Barkai and Danny Ben-Zvi Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel Spemann’s experiments and the scaling of pattern with size in the amphibian embryo From the early days of embryology, biologists have marveled at the remarkable consistency of the develo- ping body plan. In 1942, Conrad Waddington put forward the concept of canalization, referring to the invariance of the wild-type phenotype in the face of genetic or environmental perturbations [1]. Since then, extensive research has been devoted to understand the origins and evolutionary implications of this funda- mental property of developing organisms [2]. The plasticity of embryonic development, with its ability to overcome extreme perturbations, was demon- strated most dramatically in two classic experiments performed by Hans Spemann at the beginning of the 20th century [3–5] (Fig. 1A,B). In 1903, Spemann used a thin baby hair to bisect a cleaving newt embryo into dorsal and ventral halves. Remarkably, dorsal-halved, but not ventral-halved, embryos healed and developed into normal, albeit smaller tadpoles. Twenty years later, in 1924, Hilde Mangold joined Spemann to perform a second fascinating experiment in which they transplanted a group of dorsal cells (‘dorsal lip’) grafted from a donor embryo into the ventral pole of a recipient embryo. Strikingly, a complete secondary axis ensued, resulting in Siamese twins. The trans- planted cells re-specified host tissues to form neural tissues and somites instead of epidermis and ventral– posterior mesoderm. The transplanted cells themselves only contributed to a fraction of the secondary axis, Keywords Admp; BMP; Chordin; control theory; development; dorsal-ventral; feedback; morphogen gradient; scaling; Xenopus Correspondence N. Barkai, Department of Molecular Genetics, Weizmann Institute of Science, PO Box 26, Rehovot 76100, Israel Fax: +972 8 934 4108 Tel: +972 8 934 4429 E-mail: naama.barkai@weizmann.ac.il (Received 10 October 2008, revised 4 December 2008, accepted 11 December 2008) doi:10.1111/j.1742-4658.2008.06854.x We discuss mechanisms that enable the scaling of pattern with size during the development of multicellular organisms. Recently, we analyzed scaling in the context of the early Xenopus embryo, focusing on the determination of the dorsal–ventral axis by a gradient of BMP activation. The ability of this system to withstand extreme perturbation was exemplified in classical experiments performed by Hans Spemann in the early 20th century. Quan- titative analysis revealed that patterning is governed by a noncanonical ‘shuttling-based’ mechanism, and defined the feedback enabling the scaling of pattern with size. Robust scaling is due to molecular implementation of an integral-feedback controller, which adjusts the width of the BMP mor- phogen gradient with the size of the system. We present an ‘expansion– repression’ feedback topology which generalizes this concept for a wider range of patterning systems, providing a general, and potentially widely applicable model for the robust scaling of morphogen gradients with size. Abbreviations Admp, anti-dorsalizing morphogenic protein; BMP, bone morphogenic protein. 1196 FEBS Journal 276 (2009) 1196–1207 ª 2009 The Authors Journal compilation ª 2009 FEBS Fig. 1. Scaling of the BMP gradient along the dorsal–ventral VASCULOGENESIS AND ANGIOGENESIS – FROM EMBRYONIC DEVELOPMENT TO REGENERATIVE MEDICINE Edited by Dan T. Simionescu and Agneta Simionescu Vasculogenesis and Angiogenesis – From Embryonic Development to Regenerative Medicine Edited by Dan T. Simionescu and Agneta Simionescu Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Marina Jozipovic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright Norph, 2011. Used under license from Shutterstock.com First published October, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Vasculogenesis and Angiogenesis – From Embryonic Development to Regenerative Medicine, Edited by Dan T. Simionescu and Agneta Simionescu p. cm. ISBN 978-953-307-882-3 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Developmental Biology 1 Chapter 1 Human Embryonic Blood Vessels: What Do They Tell Us About Vasculogenesis and Angiogenesis? 3 Simona Sârb, Marius Raica and Anca Maria Cîmpean Chapter 2 Cardiac Vasculature: Development and Pathology 15 Michiko Watanabe, Jamie Wikenheiser, Diana Ramirez-Bergeron, Saul Flores, Amir Dangol, Ganga Karunamuni, Akshay Thomas, Monica Montano and Ravi Ashwath Chapter 3 Vascular Growth in the Fetal Lung 49 Stephen C. Land Chapter 4 Apelin Signalling: Lineage Marker and Functional Actor of Blood Vessel Formation 73 Yves Audigier Part 2 Endothelial Progenitor Cells 97 Chapter 5 Regulation of Endothelial Progenitor Cell Function by Plasma Kallikrein-Kinin System 99 Yi Wu and Jihong Dai Chapter 6 Vasculogenesis in Diabetes-Associated Diseases: Unraveling the Diabetic Paradox 107 Carla Costa Part 3 Cancer Research 131 Chapter 7 Modeling Tumor Angiogenesis with Zebrafish 133 Alvin C.H. Ma, Yuhan Guo, Alex B.L. He and Anskar Y.H. Leung VI Contents Chapter 8 Therapeutic and Toxicological Inhibition of Vasculogenesis and Angiogenesis Mediated by Artesunate, a Compound with Both Antimalarial and Anticancer Efficacy 145 Qigui Li, Mark Hickman and Peter Weina Part 4 ... prepare for swallowing and breathing out of the uterus 6/18 Embryonic Development Development of the Embryonic Disc Formation of the embryonic disc leaves spaces on either side that develop into... pregnancy typically requires several ovulation cycles to achieve Pre -Embryonic Development Ovulation, fertilization, pre -embryonic development, and implantation occur at specific locations within... was sitting on top of the flat embryo, envelops the embryo as it folds 13/18 Embryonic Development Embryonic Folding Embryonic folding converts a flat sheet of cells into a hollow, tube-like structure