东大生科发育生物学

1、 Development - a relatively slow process of progressive change Developmental biology - a discipline that studies embryonic and other developmental processesQuestions of developmental biology Fundamental question how a fertilized egg is transformed into a complex multicellular organism General questi

2、onsGeneral questions Differentiation - the generation of cellular diversity Morphogenesis - the creation of ordered form Growth reproduction Evolution Environmental integrationFeatures of developmental biology Questions asked “becoming” rather than “being” An integrated discipline Overview and gener

3、al concepts The stages of animal development Fate mapping Cell specification Morphogenesis and cell adhesion Mathematical modeling of developmentA representative life cycle (The development of a frog )development: from fertilization through deathMSMitosis-promoting factorearly blastomeressomatic cel

4、ls（卵裂球）Types of cell movements during gastrulation 内陷内卷外包内移层裂The germ cells are shown as not arising from any of the germ layers. Three germ layers that give rise to the specific organ systemsFate mapping Map the larval or adult structure onto the region of the embryo(Which portions of the embryo be

5、come which larval or adult structure)Fate maps of different vertebrates at the early gastrula stage原肠胚Ways to generate fate maps Observing living embryo Radioactive labeling Fluorescent dye marking Genetic marking3HNormal cultureGrow for some timeautoradiographyFate mapping by radioactive labelingDo

6、nor embryoHost embryo (A) Specific cells of a zebrafish embryo were injected with a fluorescent dye that will not diffuse from the cells. (B) After formation of the central nervous system had begun, the fluorescent dye is seen in particular cells that generate the forebrain and midbrain. Fate mappin

7、g using a fluorescent dye The quail cells have a single large nucleolus (staining purple), distinguishing them from the diffuse nuclei of the chick.Genetic markers as cell lineage tracersQuail cells can be seen by using an antibody to quail-specific proteins.?Neural crest cell migrationCell migratio

8、n during development - one of the most important contributions of fate mappingchick resulting from embryo transplantationNeural tube formation in the chick embryoCell specification and developmental patterns Overt differentiation is preceded by a covert commitment to certain fate The process of comm

9、itment consists of specification and determination The fate of a cell is said to be specified when it is capable of differentiating autonomously when placed in a neutral environment The fate of a cell is said to be determined when it is capable of differentiating autonomously even when placed into a

10、nother region of the embryoSpecificationdeterminationdifferentiationReversibleCovert changeIrreversibleCovert changeIrreversibleOvert change commitmentRelations between cell fate, cell specification and cell determinationThree Modes of cell specification Autonomous specification Conditional specific

11、ation Syncytial specificationAutonomous specification in the early tunicate embryo柄海鞘Diagram of the isolation procedure. Localization of acetylcholinesterase in an intact tunicate larva. The progeny of the B4.1 blastomere pair The remaining 6/8 of the embryoIsolated b4.1 blastomeres produce muscle t

12、issueModified b4.2 cells produce muscle cells as well as their normal ectodermal progenyAutonomous specification Specification by differential acquisition of certain morphogenetic determinants in the egg cytoplasm Produces mosaic development; cells cannot change fate if a blastmere is lost Often use

13、d by invertebrates to determine cell fate(A)(B)囊胚 In armadillo, the original embryo always splits into four separate groups, each of which forms its own embryo犰狳Weismanns germ plasm theory （1893）Drieschs demonstration of regulative development in sea urchin embryoIn conditional specification, cell-c

14、ell interactions may be indirectNote:e.g., cell fates can also be specified by a concentration gradient of morphogenHydras regenerationA gradient model explaining conditional cell specificationActivin is responsible for converting animal hemisphere cells into mesodermXenopusA gradient of activin cau

15、ses different gene expression in Xenopus animal cap cells. Conditional specification Specified by interactions between cells. Relative positions are important Correlates with regulative development: allows cells to acquire different functions used by all vertebrates and few invertebrates to determin

16、e cell fateSyncytial specification in the fruit flySyncytial specification Cell fates are determined by morphogen gradients within the egg cytoplasm Characteristic of most insectsNotes to cell specification No embryo uses only one mechanism to specify its cells Insects such as Drosophila use all thr

17、ee modes of specification to commit their cells to particular fates.Morphogenesis and cell adhesionDevelopment involves not only the differentiation of cells, but also their ordered organization into multicellular structures such as tissues and organs (morphogenesis)Major questions concerning morpho

18、genesis How are tissues formed from populations of cells? How are organs constructed from tissues? How do organs achieve polarity? How do organs form in particular locations, and how do migrating cells reach their destinations? Figure 12.28. Development of the human retina Cell behavior that brings

19、about morphogenesis Cell divisions Cell movement Cell shape change Cell growth, cell death Changes in the cell surfaceAnalysis of morphogenesis began with the experiment of Holtfreter in 1955Reaggregation of cells from amphibian neurulae (神经胚)Sorting out and reconstruction of spatial relationships i

20、n aggregates of embryonic amphibian cells不同胚层Conclusion: different cell types can sort themselves into specific regions to create tissues and organsWhy?Differential adhesion hypothesis- a model to explain patterns of cell sorting If connection strength of A-A A-B , sorting will occur, with A becomin

21、g central If A-AA-B, ? Cell-cell adhesions form hierarchy If A is internal to B, and B is internal to C, then A will always be internal to CHierarchy of cell sortingCadherins（钙粘素） Cacium-dependent cell adhesion molecules Major classes： E(epithelial)- cadherin: expressed on all early mammalian embryo

22、nic cells, later restricted to epithelial tissues N(neural)- cadherin: expressed on developing cells of CNS Cadherin-mediated cell adhesion. Cadherins are associated with three types of catenins. The catenins can become associated with the actin microfilament system within the celllocalize E-cadheri

23、n (B) and N-cadherin (C) in the same transverse section of an embryonic mouse hindbrain. Localization of two different cadherins during the formation of the mouse neural tubeLeft: the embryo that develops from an oocyte injected with an antisense oligo against a maternally inherited cadherin mRNA, R

24、ight: control embryos Cadherins maintains cohesion between developing cellsThe left side of the Xenopus embryo were injected with mutated N-cadherin mRNAThe importance of N-cadherin in the separation of neural and epidermal ectodermMathematical medeling of developmentThe red lines indicate the order

25、 that leaves grow up the stem.Leaf arrangement, with numbers of successive leaves numbered. 0, 1, 1, 2, 3, 5, 8, 13, 21, 34, 55, 89, 144, Fibonacci sequence: Examples of phyllotaxis. (A) Schematic diagram of leaf arrangement, with numbers of successive leaves numbered. (B) Example of Aloe polyphylla

26、 (多叶芦荟) displaying an angle of 137.5 degrees between adjacent leaves, as indicated by the red lines. (C) Daisy with 21 petals (21 is a Fibonacci number) Sunflower： there is a pattern involving two sets of spirals that criss-cross, with one set of spirals turning clockwise, and the other turning coun

27、ter-clockwise. At each location where two spirals cross a seed can be found. The number of spirals turning counter-clockwise happens to be 55, and the number of clockwise spirals happens to be 89 both Fibonacci numbers Fibonacci numbers in nature Turing model （reaction-diffusion model）Mathematical d

28、escription of Turing systemThe finding of type VI wave is the major achievement of Turings analyses (explain how spatial patterns arise autonomously, i.e. explain pattern formation without a preformed pattern ). Turings system yields six potential steady states. (A) The conditions of the model yield

29、 a peak of the slowly diffusing activator (P) and a lower peak of the rapidly diffusing inhibitor (S) at the same location. (B) The distribution of the morphogens is initially random (no prefromed pattern). As the concentration of P increases locally, it stimulates the production of more of itself (called “autocatalysis”), as well as of S which diffuses away quickly to inhibit more peaks of P from forming, resulting in a series of P peaks (red arrows) at regular intervals whose positions don