VI 胚層發(fā)育與器官系統(tǒng)發(fā)生(I)

1、developmental biologychapter 6: development of the vertebrate germ layers and organogenesis (i)development of the vertebrate germ layers and organogenesis1 development of the vertebrate germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development

2、of the nervous system 2.1 the specification of neural cell ( neuron or glial cell) identity2.2 migration of neurons and the guided outgrowth of axons toward their target cells2.3 synapse formation and refinement3 the limb development3.1 formation of the limb bud and limb outgrowth3.2 generation of t

3、he proximal-distal axis of the limb3.3 specification of the anterior-posterior limb axis 3.4 generation of the dorsal-ventral axis 3.5 coordinating the three axes 3.6 development of the digits 4 formation of internal organs, blood vessels, lungs, kindney, heart, and teeth (option)development of the

4、vertebrate germ layers and organogenesisdevelopment of the vertebrate germ layers and organogenesis1 development of the vertebrate germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development of the nervous system 2.1 the specification of neural c

5、ell ( neuron or glial cell) identity2.2 migration of neurons and the guided outgrowth of axons toward their target cells2.3 synapse formation and refinementmajor derivatives of the ectoderm germ layerdorsalventralmajor derivatives of the ectoderm germ layerdorsalventralmajor derivatives of the mesod

6、erm germ layerthe major function of the embryonic endoderm is to construct the linings of two tubes within the vertebrate body the digestive tube and its derivatives (liver, gallbladder, and pancreas)the major function of the embryonic endoderm is to construct the linings of two tubes within the ver

7、tebrate body the respiratory tubethe digestive tube and its derivatives (liver, gallbladder, and pancreas)development of the germ layers and organogenesis1 development of the germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development of the nerv

8、ous system 2.1 the specification of neural cell ( neuron or glial cell) identity2.2 migration of neurons and the guided outgrowth of axons toward their target cells2.3 synapse formation and refinementdevelopment of the nervous systemn the nervous system is the most complex of all the organ systems i

9、n the animal embryo. in mammals, for example, billions of nerve cells, or neurons, develop a highly organized pattern of connections, creating the neuronal network that makes up the functioning brain and the rest of the nervous system.n the nervous system contains many hundreds of different types of

10、 neurons, varying in sizes, shapes and functions. the nervous system can only function properly if the neurons are correctly connected to one another, thus a central question in nervous system development is how the connections between neurons with each other and with other target cells develop with

11、 the appropriate specificity.development of the nervous systemn neurons connect with each other and with other target cells, such as muscle, at specilized junctions known as synapses（突觸突觸）. n a neuron receives input from other neurons through its highly branched dendrites, and generate a nerve impul

12、se at the cell body. this nerve impulse is then conducted along the axon to the axon terminal, which makes a synapse with the dendrites or cell body of another neuron or with the surface of a muscle cell.n the dendrites and axon terminals of individual neurons can be extensively branched, and a sing

13、le neuron in the cns can receive as many as 100,000 different input.development of the nervous systemn development of the nervous system involve neuronal cell differentiation, morphogenesis, and migrationn the overall process of nervous-system development can be divided up into four major stages:the

14、 specification of neural cell (neuron or glial cell) identitythe migration of neurons and the outgrowth of axons to their targetsthe formation of synapses between neurons with each other and with other tragets, such as muscle etcthe refinement of synaptic connections through the elimination of axon

15、branches and cell deathdevelopment of the germ layers and organogenesis1 development of the germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development of the nervous system 2.1 the specification of neural cell ( neuron or glial cell) identity2.2

16、 migration of neurons and the guided outgrowth of axons toward their target cells2.3 synapse formation and refinementdevelopment of the germ layers and organogenesis1 development of the germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development

17、of the nervous system 2.1 the specification of neural cell ( neuron or glial cell) identity2.2 migration of neurons and the guided outgrowth of axons toward their target cells2.3 synapse formation and refinementthe presumptive nervous system is specified early in embryonic development in both invert

18、ebrates and vertebratesthe presumptive nervous system is specified early in embryonic development in both invertebrates and vertebratesspecification of the neuronal precursors involves lateral inhibition in both invertebrates and vertebratesn in drosophila, the neurectoderm is subdivided along the a

19、p and dv axes into a precise orthogonal （直角直角） pattern of proneural clusters. within each cluster, cell-cell interactions through lateral inhibition direct one cell into a neural precursor or neuroblast fate. the rest become epidermal cells.n as in drosophila, lateral inhibition specifies single cel

20、ls as neuronal precursors in the vertebrate nervous system.further development of neurons from neuronal precursors involves asymmetric cell division in drosophilaafter specification, the drosophila neuroblasts delaminate from the neurectodermal epithelium to lie adjacent to its inner, or basal face,

21、 and then behave as a stem cells. each neuroblast divides asymmetrically to give an apical cell, which remains a neural stem cell, and a smaller basal cell, the ganglion mother cell (gmcs), which will differentiate into neurons.the localized protein determinants in neuroblasts specify the orientatio

22、n of cell division and daughter cell fate:numb: the ganglion mother cell fateinsc/pins: the orientation of the plane of cell divisionbazooka prospero/miranda numb the pattern of differentiation of cells along the dv axis of the spinal cord depends on ventral and dorsal signalsn there is a distinct d

23、orso-ventral pattern in the developing spinal cord. specifically, different types of neurons differentiate along the dv axis. motor neurons and interneurons are located ventrally, whereas commissural neurons （連合神經(jīng)元連合神經(jīng)元）differentiate in the dorsal regionn differentiation of neuronal subtypes along t

24、he dv axis is determined by sonic hedgehog protein (shh), the ventral signal secreted by the notochord, and bmps, the dorsal signal from the dorsal epidermal ectodermbmp signalshh signalthe neurons of the spinal cord are given their identity by exposure to the gradients of two signal proteinsthe gra

25、ded signal proteins cause different transcriptional factors to be activated in the nuclei of the neuronal cells, depending on their position along the dv axisa graded sonic hedgehog signal patterns different neuronal types in the ventral region of the spinal cord through regulating two classes of ho

26、meodomain protein genesthe distribution pattern of the signal proteins and homeodomain proteins in chick neural tube along the dv axisbmpsshhpax7pax6nkx6.1f: chick neural tubeg: in situ hybridization for 3 homeodomain proteins. where nkx6.1 and pax6 overlap, the motor neurons become specified.mnsmns

27、development of the germ layers and organogenesis1 development of the germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development of the nervous system 2.1 the specification of neural cell ( neuron or glial cell) identity2.2 migration of neurons a

28、nd the guided outgrowth of axons toward their target cells2.3 synapse formation and refinementthe developmental process for establishing the functioning network of neuronsn migration of immature neuronsthe migration of neural crest cellswhat controls the the neural crest migration?n outgrowth of axo

29、ns toward their targetshow is the growth of axons guided?what are the mechanisms underlying the axon guidance? the functioning neuronal network involves both migration of immature neurons and outgrowth of axons toward their targets (i)n neural crest cells and axonal outgrowth of neurons share the pr

30、operty of having to migrate far from their source of origin to specific places in the embryothey both need to recognize cues (信號(hào)信號(hào)) to begin this migration, and respond to signals that guide them along specific routes to their final destinationmany of the signals recognized by neural crest cells and

31、 by axonal growth cones are the same the functioning neuronal network involves both migration of immature neurons and outgrowth of axons toward their targets (ii) the functioning neuronal network involves both migration of immature neurons and outgrowth of axons toward their targets (i)n migration o

32、f immature neuronsthe migration of neural crest cellswhat controls the the neural crest migration?n outgrowth of axons toward their targetshow is the growth of axons guided?what are the mechanisms underlying the axon guidance? dorsalventralthe neural crest cells migrate extensively to generate a lar

33、ge number of differentiated cell types the fate of the neural crest cells depends, to a large degree, on where they migrate to and settlethe neural crest can be divided into 4 main domains (overlapping), each with characteristic derivatives and functionsl the cranial (cephalic 頭部頭部) neural crest cel

34、ls： the cartilage, bone, cranial neurons, glia and connective tissues of the facel the trunk neural crest cells the dorsal root ganglia containing the sensory neurons the sympathetic ganglia, the adrenal medulla, melanocytes etcl the vagal (neck) and sacral (骶骶) neural crest cells parasympathetic ga

35、nglia of the gutl the cardiac neural crest cells melanocytes, neurons, cartilage, and connective tissues the entire muscular-connective tissue wall of the large arteriesneural crest cell migration is controlled by environmental cues and adhensive differences (i)n the adhensive differences the dynami

36、c expression of n-cadherin in neural crest cells is essential for the initiation of neural crest cells, the segragation of the neural crest cells from the neural tube. ( n-cadherin is expressed in neural crest cells prior to migration, and after migration. but, down-regulation of n-cadherin expressi

37、on at the time of migration, and turning off of n-cadherin expression during migration)constitutive expression of n-cadherin dramatically supresses the movement of the neural crest cells from the neural tube.neural crest cell migration is controlled by environmental cues and adhensive differences (i

38、i)n the environmental cues (cues from the extracellular matrices) migration-promoting proteins : fibronectin (纖維連接蛋白纖維連接蛋白), laminin (層粘連蛋白層粘連蛋白), various collagen molecules, and proteoglycans etc ( by binding to integrin in neural crest cells) migration-impeding proteins : the ephrin proteins (by b

39、inding to eph receptor in neural crest cell membranes)ephrin functions as a repulsive signal for neural crest cell migrationa: negative correlation between regions of the ephrin in the sclerotome生骨節(jié) and the presence of neural crest cellsb: when neural crest cells are plated on fibronectin-containing

40、 matrices with alternating stripes of ephrin, they bind to thoe regions lacking ephrinc: composite scheme showing the migration of spinal cord neural crest cells and motor neurons through the ephrin-deficient anterior regions of the sclerotomes the functioning neuronal network involves both migratio

41、n of immature neurons and outgrowth of axons toward their targets (i)n migration of immature neuronsthe migration of neural crest cellswhat controls the the neural crest migration?n outgrowth of axons toward their targetshow is the growth of axons guided?what are the mechanisms underlying the axon g

42、uidance? the growth cone controls the path taken by the growing axon dendrites are the fine, branching extensions of the neuron that are used to pick up electric impulses from other cells. in human, the average cortical neuron connects with 10,000 other neural cells. axon is a continuous extension o

43、f the nerve cell body which may be several feet long. neurons make functional connections with their targets through outgrowth of axons. the outgrowth of the axon is guided by the growth cone at the axon tip the growth cone moves by the elongation and contraction of pointed filopodia called microspi

44、kes (微突微突). these microspikes contain actin microfilaments, which are oriented parallel to the long axis of the axon.the growth cone controls the path taken by the growing axonactintubulinthe growth cone both moves and senses its environment, functioning as both locomotor and sensory apparatusn in g

45、eneral, the growth cone moves in the direction in which its filopodia make the most stable contacts with other cells and with the extracellular matrix. n the extracellular signals can bind to receptors on the growth cone surface, and influence its direction of migration. the extension and retraction

46、 of filopodia involves the assembly and disassembly of the actin cytoskeleton. members of a family of intracellular signaling proteins, the ras-related gtpases, are involved in the reorganization of the actin cytoskeleton: activation of rho cause growth cones to stop extendingrac and cdc42 are invol

47、ved in growth-cone extensionn how growth cones transduce extracellular signals so as to extend or collapse filopodia is not fully understood.the growth cone controls the path taken by the growing axonaxon growth cones are guided by two main types of cueattractive and repulsive signals n chemoattract

48、ant proteins netrins cadherinsn chemorepellants proteinssemaphorinsephrinslit proteinsn these signal proteins often function as both attractants and repellants, depending on the cellular contextaxon growth cones are guided by two main types of cue-attractive and repulsivenetrin-1 is a key attractant

49、 produced in the floor plate and in the middlelinemotor neurons from the spinal cord make muscle specific connections controlled by epha signalingdevelopment of the germ layers and organogenesis1 development of the germ layers1.1 ectoderm1.2 paraxial and intermediate mesoderm1.3 lateral plate mesoderm and endoderm2 development of the nervous system 2.1 the specification of neural cell ( neuron or glial cell) identity2.2 migration of neurons and the guided outgrowth of axons toward t