第十五章-细胞分化与胚胎发育-北大陈建国细胞生物学.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,1,第,15,章 细胞分化和胚胎发育,Cell differentiation and embryonic development,The four essential cell processes that allow a multicellular organism to be made,which produces,many cells from one;,which coordinate the behavior,of each cell with that of its neighbors;,or differentiation,which creates cells with different characteristics at different positions,；,which rearranges the cells to form structured tissues and organs.,2,15-1.UNIVERSAL MECHANISMS OF ANIMAL DEVELOPMENT,Homologous proteins functioning interchangeably in the development of mice and flies,4,The scanning electron micrographs show a patch of eye tissue on the leg of a fly resulting from misexpression of,Drosophila Eyeless(top),and of,squid Pax6(bottom),.The right panel shows,at lower magnification,the entire eye of a normal Drosophila,5,Animals Share Some Basic Anatomical Features,Sea urchin gastrulation,.A fertilized egg divides to produce a blastulaa hollow sphere of epithelial cells surrounding a cavity.Then,in the process of gastrulation,some of the cells tuck into the interior to form the gut and other internal tissues.(A)Scanning electron micrograph showing the initial intucking of the epithelium.,6,(B)A group of cells break loose from the epithelium to become mesoderm.(C)These cells then crawl over the innerface of the wall of the blastula.(D)Meanwhile,epithelium is continuing to tuck inward to become endoderm.(E and F)The invaginating endoderm extends into a long gut tube.(G)The end of the gut tube makes contact with the wall of the blastula at the site of the future mouth opening.Here the ectoderm and endoderm will fuse and a hole will form.,7,8,The basic animal body plan,with a sheet of ectoderm on the outside,a tube of endoderm on the inside,and mesoderm sandwiched between them.,9,Multicellular Animals Are Enriched in Proteins Mediating Cell,Interactions and Gene Regulation,C.elegans:20,000 genes Drosophila:14,000 genes,Human:25,000 genes,About 50%of the genes in each of these species have clearly recognizable homologs in one or both of the other two species,Multicellular animal,As many as 2000 C.elegans genes encode cell surface receptors,cell adhesion proteins,and ion channels that are either not present in yeast or present in much smaller numbers.,gene regulatory proteins:these DNA-binding proteins are much more numerous in the,C.elegans,genome than in yeast.,The basic helixloophelix family has 41 members in,C.elegans,84 in,Drosophila,131 in humans and only 7 in yeast,10,Regulatory DNA Defines the Program of Development,How regulatory DNA defines the succession of gene expression patterns in development,11,Cell lineage tracing in the early chick embryo,.,The pictures in the top row are at low magnification and show the whole embryo;the pictures below are details,showing the distribution of labeled cells.The tracing experiment reveals complex and dramatic cell rearrangements.,Manipulation of the Embryo Reveals the Interactions Between Its Cells,12,Some striking results obtained by experimental embryology,13,Studies of Mutant Animals Identify the Genes That Control Developmental Processes.,A Cell Makes Developmental Decisions Long Before It Shows a Visible Change.,14,A Cell Makes Developmental Decisions Long Before It Shows a Visible Change,Prospective thigh tissue grafted into the tip of a chick wing bud forms toes.(After J.W.Saunders et al.,Dev.Biol.1:281301,1959.With permission from Academic Press.),15,Chick embryos at 6 days of incubation,showing the limb buds stained by in situ hybridization with probes to detect expression of the Tbx4,Tbx5,and Pitx1 genes,all coding for related gene regulatory proteins.The cells expressing Tbx5 will form a wing;those expressing Tbx4 and Pitx1 will form a leg.Pitx1,when artificially misexpressed in the wing bud,causes the limb to develop with leg-like characteristics.,16,Inductive Signals Can Create Orderly Differences Between Initially,Identical Cells,17,Some Signal Proteins That Are Used Over and Over Again as Inducers in Animal Development,18,Sister Cells Can Be Born Different by an Asymmetric Cell Division,Centrosomes and Neural Stem Cells,The dominant force of Centrobin in centrosome asymmetry,19,apical(yellow)and basal(pink)cortical crescents are established,Centrobin(CNB),20,21,Positive Feedback Can Create Asymmetry Where There Was None,Before,Genesis of asymmetry through positive feedback.,In this example,two cells interact,each producing a substance X that acts on the other cell to inhibit its production of X,an effect known as lateral inhibition.,22,Morphogens Are Long-Range Inducers That Exert Graded Effects,Sonic hedgehog as a morphogen in chick limb development.,(A)Expression of the Sonic hedgehog gene in a 4-day chick embryo,shown by in situ hybridization.The gene is expressed in the midline of the body and at the posterior border of each of the two wing buds.Sonic hedgehog protein spreads out from these sources.,(B)Normal wing development.(C)A graft of tissue from the polarizing region causes a mirror-image duplication of the pattern of the host wing.The type of digit,that develops is thought to be dictated by the local concentration of Sonic hedgehog protein;different types of digit(labeled 2,3,and 4)therefore form according to their distance from a source of Sonic hedgehog.,23,Extracellular Inhibitors of Signal Molecules Shape the Response,to the Inducer,24,Developmental Signals Can Spread Through Tissue in Several,Different Ways,Figure 22-16,Molecular Biology of the Cell,(Garland Science 2008),25,Initial Patterns Are Established in Small Fields of Cells and,Refined by Sequential Induction as the Embryo Grows,26,15-2.CAENORHABDITIS ELEGANS:DEVELOPMENT FROM,THE PERSPECTIVE OF THE INDIVIDUAL CELL,As an adult,C.elegans consists of only about 1000 somatic cells and 10002000,germ cells(exactly 959 somatic cell nuclei plus about 2000 germ cells in one sex;,exactly 1031 somatic cell nuclei plus about 1000 germ cells in the other),27,Cell Fates in the Developing Nematode Are Almost Perfectly,Predictable,The lineage tree for the cells that form the gut(the intestine)of C.elegans,28,Products of,Maternal-Effect Genes,Organize the Asymmetric,Division of the Egg,Asymmetric divisions segregating P granules into the founder cell of the C.elegans germ line.The micrographs in the upper row show the pattern of cell divisions,with cell nuclei stained blue with a DNA-specific fluorescent dye;below are the same cells stained with an antibody against P granules.These small are distributed randomly throughout the cytoplasm in the unfertilized egg(not shown).After fertilization,at each cell division up to the 16-cell stage,both they and the intracellular machinery that regulates their asymmetric localization are segregated into a single daughter cell.,Par proteins,29,Progressively More Complex Patterns Are Created by CellCell,Interactions,The pattern of cell divisions in the early C.elegans embryo,indicating the names and fates of the individual cells,Notch,Cell signaling pathways controlling assignment of differentcharacters to the cells in a four-cell nematode embryo,30,Selected Cells Die by Apoptosis as Part of the Program of Development,The control of cell numbers in development depends on cell death as well as cell division.A C.elegans hermaphrodite generates 1030 somatic cell nuclei in the,course of its development,but 131 of the cells die.,31,15-3.DROSOPHILA AND THE MOLECULAR GENETICS OF,PATTERN FORMATION:GENESIS OF THE BODY PLAN,Cell number;Genes;noncoding DNA;,gene duplications of vertebrate genomes,32,The Insect Body Is Constructed as a Series of Segmental Units,33,The origins of the Drosophila body segments during embryonic development.,34,The segments of the Drosophila larva and their correspondence with regions of the blastoderm.,35,Development of the Drosophila egg from fertilization to the cellular blastoderm stage,.(A)Schematic drawings.(B)Surface view an optical-section photograph of blastoderm nuclei undergoing mitosis at the transition from the syncytial to the cellular blastoderm stage.Actin is stained green,chromosomes orange.,36,Fate map of a Drosophila embryo at the cellular blastoderm stage,37,Genetic Screens Define Groups of Genes Required for Specific,Aspects of Early Patterning,The domains of the anterior,posterior,and terminal systems of egg-polarity genes,.Upper diagrams show the fates of the different regions of the egg/early embryo and indicate(in white)the parts that fail to develop if the anterior,posterior,or terminal system is defective.Middle row shows schematically the appearance of a normal larva and of mutant larvae that are defective in a gene of the anterior system(Bicoid),of the posterior system(Nanos),or of the terminal system(Torso).The bottom row of drawings shows the appearances of larvae in which none or only one of the three gene systems is functional.Inactivation of a particular gene system causes loss of the corresponding set of body structures;the body parts that form correspond to the gene systems that remain functional.Note that larvae with a defect in the anterior system can still form terminal structures at their anterior end,but these are of the type normally found at the rear end of the body rather than the front of the head.,38,Interactions of the Oocyte With Its Surroundings Define the Axes,of the Embryo:the Role of the Egg-Polarity Genes,39,The organization of the four egg-polarity gradient systems(,maternal-effect genes,).The receptors Toll and Torso are distributed all over the membrane;the coloring in the diagrams on the right indicates where they become activated by extracellular ligands.,The Role of the Egg-Polarity Genes,40,The Dorsoventral Signaling Genes Create a Gradient of a Nuclear,Gene Regulatory Protein,The concentration gradient of Dorsal protein(like NF-kabaB)in the nuclei of the blastoderm,as revealed by an antibody.Dorsally,the protein is present in the cytoplasm and absent from the nuclei;ventrally,it is depleted in the cytoplasm and concentrated in the nuclei(Toll receptor on the ventral side of the egg controls the distribution of Dorsal).,41,Morphogen gradients patterning the dorsoventral axis of the embryo.(A)The gradient of Dorsal protein defines three broad territories of gene expression,marked here by the expression of three representative genesDpp,Sog,and,Twist,.(B)Slightly later,the cells expressing Dpp and Sog secrete,respectively,the signal proteins Dpp(a TGFb family member)and Sog(an antagonist of Dpp).These two proteins diffuse and interact with one another(and with certain other factors)to set up a gradient of Dpp activity that guides a more detailed patterning process.,Dpp and Sog Set Up a Secondary Morphogen Gradient to Refine,the Pattern of the Dorsal Part of the Embryo,42,Origin of the mesoderm from cells expressing Twist,.Embryos were fixed at successive stages,crosssectioned,and stained with an antibody against the Twist protein,a gene regulatory protein of the bHLH family.The cells that express Twist move into the interior of the embryo to form mesoderm.,The Dorsoventral Signaling Genes Create a Gradient of a Nuclear,Gene Regulatory Protein,43,The Insect Dorsoventral Axis Corresponds to the Vertebrate,Ventrodorsal Axis,Dpp:a member of the TGFb superfamily of signal molecules that is also important in vertebrates;,Sog:a homolog of the vertebrate protein chordin.,It is striking that a Dpp homolog,BMP4,and chordin work together in vertebrates in the same way as do Dpp and Sog in Drosophila.,44,45,Three Classes of Segmentation Genes Refine the,AnteriorPosterior Maternal Pattern and Subdivide the Embryo,间隙基因 成对控制基因 体节极性基因,Examples of the phenotypes of mutations affecting the three types of segmentation genes,46,The Localized Expression of Segmentation Genes Is Regulated by,a Hierarchy of Positional Signals,The regulatory hierarchy of egg-polarity,gap,segmentation,and homeotic selector genes,.The photographs show expression patterns of representative examples of genes in each category,47,48,49,50,HOMEOTIC SELECTOR GENES AND THE,PATTERNING OF THE ANTEROPOSTERIOR AXIS,The Hox Code Specifies AnteriorPosterior Differences,A homeotic mutation.The fly shown here is an Antennapedia mutant.,What is the basic construction mechanism common to all the objects of the given class?,How is this mechanism modified to give the observed variations?,Figure 22-43,Molecular Biology of the Cell,(Garland Science 2008),51,Figure 22-44,Molecular Biology of the Cell,(Garland Science 2008),52,Figure 22-45,Molecular Biology of the Cell,(Garland Science 2008),53,Figure 22-46,Molecular Biology of the Cell,(Garland Science 2008),54,Figure 22-47,Molecular Biology of the Cell,(Garland Science 2008),55,Figure 22-48,Molecular Biology of the Cell,(Garland Science 2008),56,Figure 22-49,Molecular Biology of the Cell,(Garland Science 2008),57,Figure 22-50a,Molecular Biology of the Cell,(Garland Science 2008),58,Figure 22-50b,Molecular Biology of the Cell,(Garland Science 2008),59,Figure 22-51,Molecular Biology of the Cell,(Garland Science 2008),60,Figure 22-52a,Molecular Biology of the Cell,(Garland Science 2008),61,Figure 22-52b,Molecular Biology of the Cell,(Garland Science 2008),62,Figure 22-53,Molecular Biology of the Cell,(Garland Science 2008),63,Figure 22-54a,Molecular Biology of the Cell,(Garland Science 2008),64,Figure 22-54b,Molecular Biology of the Cell,(Garland Science 2008),65,Figure 22-55,Molecular Biology of the Cell,(Garland Science 2008),66,Figure 22-56,Molecular Biology of the Cell,(Garland Science 2008),67,Figure 22-57,Molecular Biology of the Cell,(Garland Science 2008),68,Figure 22-57a,Molecular Biology of the Cell,(Garland Science 2008),69,Figure 22-57b,Molecular Biology of the Cell,(Garland Science 2008),70,Figure 22-58,Molecular Biology of the Cell,(Garland Science 2008),71,Figure 22-59,Molecular Biology of the Cell,(Garland Science 2008),72,Figure 22-60a,Molecular Biology of the Cell,(Garland Science 2008),73,Figure 22-60b,Molecular Biology of the Cell,(Garland Science 2008),74,Figure 22-61,Molecular Biology of the Cell,(Garland Science 2008),75,Figure 22-62,Molecular Biology of the Cell,(Garland Science 2008),76,Figure 22-63,Molecular Biology of the Cell,(Garland Science 2008),77,Figure 22-64a,Molecular Biology of the Cell,(Garland Science 2008),78,Figure 22-64b,Molecular Biology of the Cell,(Garland Science 2008),79,Figure 22-65,Molecular Biology of the Cell,(Garland Science 2008),80,Figure 22-66,Molecular Biology of the Cell,(Garland Science 2008),81,Figure 22-66a,Molecular Biology of the Cell,(Garland Science 2008),82,Figure 22-66b,Molecular Biology of the Cell,(Garland Science 2008),83,84,15-4.CELL MOVEMENTS AND THE SHAPING OF THE,VERTEBRATE BODY,85,The Xenopus egg and its asymmetries.(A)Side view of an egg photographed just before fertilization.,86,The Polarity of the Amphibian Embryo Depends on the Polarity of the Eg