VI 胚层发育与器官系统发生(II).ppt

《VI 胚层发育与器官系统发生(II).ppt》由会员分享，可在线阅读，更多相关《VI 胚层发育与器官系统发生(II).ppt（43页珍藏版）》请在三一办公上搜索。

1、Developmental Biology,Chapter 6:Organogenesis development of the vertebrate limb,The embryonic chick wing,The vertebrate limb development is a particularly good system in which to study pattern formation during organogenesis(I),The vertebrate limb is a complex organ with three developmental axes:the

2、 proximo-distal axis running from the base of the limb to the tip,the antero-posterior axis running parallel with the body AP axis,and the dorso-ventral axis running from the back of the hand to the palm.Thus,the limb development is a particularly good system in which to study pattern formation Sinc

3、e the limbs,unlike heart or brain,are not essential for embryonic life,one can experimentally remove or transplant parts of the developing limb,or create limb-specific mutants without interfering with the vital processes of the organism.This is good advantage of studying pattern formation in organog

4、enesis,The vertebrate limb development is a particularly good system in which to study pattern formation during organogenesis(II),The limb is a good model for studying cellular interactions within a structure containing a large number of cells,and for elucidating the role of intercellular signaling

5、in development.Recently,particular signal proteins have been identified to function in patterning along each of three limb axes:FGF family in Pr-D axial patterningSonic hedgehog(Shh)protein in A-P axial patterningWnt7a in D-V axial patterning,The vertebrate limb develops from a limb bud,3 The limb d

6、evelopment3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The anterior-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Development of the digits,Development of the vertebrate lim

7、b,3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The anterior-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Development of the digits,Development of the

8、vertebrate limb,The vertebrate limb develops from a limb bud,Proliferation of mesodermal cells from the lateral plate mesoderm causes the limb bud to bulge outward,While the lateral plate mesodermal cells generate the skeletal elements of the limb,cells from the somites provide the limbs musculature

9、,FGF10 secreted from the lateral plate mesoderm cells is the signal for limb bud induction,A:FGF10 becomes expressed in the lateral plate mesoderm of the limb bud-forming regionB:Ectopic expression of FGF10 beneath the flank ectoderm induces extra limb,FGF10,Ectopic limb,FGF10 initiates the limb bud

10、-forming interactions between the ectoderm and the mesoderm via dual signaling induction,A:FGF10 is originally expressed throughout the lateral plate mesodermB:FGF10 becomes restricted to the limb bud-forming regions,controlled by Wnt 2b and Wnt 8c respectivelyC:Dual induction between FGF10 in the m

11、esoderm and FGF8 in the apical ectoderm ridge(AER),Molecular model for the initiation of the limb bud in the chick between 48 and 54 hours of gestation,3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The anteri

12、or-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Development of the digits,Development of the vertebrate limb,Apical ectodermal ridge(AER)Progress zone(PZ),The AER is required for both the outgrowth of limb and the correct proximo-distal patter

13、ning,FGF8 is expressed in the apical ectodermal ridge(AER),FGF8 can functionally substitute for the AER,The similar results can be obtained with FGF4,indicating that FGF8/FGF4 are key signals for the AER,The mesenchyme cells:induce and sustain the AER,and determine the type of limb to be formed.The

14、AER:a major signaling center for the developing limb,and maintains the mesenchyme in a proliferating phase that enables the Pr-D growth of the limb,The proximal-distal growth of the limb bud involves interactions between the AER and the underlying mesenchyme,Role of the AER or the PZ(progress zone)i

15、n specifying the proximal-distal axis?The mechamisms underlying the PD axis specification and patterning?,How is development of the proximal-distal axis accomplished during the limb outgrowth?,Specification of proximal-distal axis is controlled by the progress zone mesenchyme,rather the AER(I),Older

16、 AER combined with younger mesoderm generates normal limbs,rather producing limbs with deletions in the middle.Younger AER combined with older mesoderm generates normal limbs,rather producing duplications of structures.,The following two transplantation experiments did not support the notion that th

17、e AER specifies the proxiomal-distal axis of the developing limbs.,An early wing-bud progress zone was transplanted to a late wing bud that had alrealy formed ulna and radiusA late wing-bud progress zone was transplanted to an early wing bud,Extra proximal structure,Lack of intermediate structures,S

18、pecification of proximal-distal axis is controlled by the progress zone mesenchyme,rather the AER(II),Two proposed models for the mesodermal specification of the Pr-D axis of the limb,a:the timing mechanism,the cell fate being determined by how long they remain in the progress zoneb:predetermination

19、 in early bud,Hox genes specify the Pr-D axis of the limb,Hox genes specify the Pr-D axis of the limb,Loss of function mutations in Hoxa-11 and Hoxd-11 lead to lacking the ulna and radius of the forelimbs,Human synpolydactyly(many fingers joined together)syndrome results from homozygosity for a muta

20、tion at the Hoxd-13 loci,3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The anterior-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Development of the dig

21、its,Development of the vertebrate limb,Zone of polarizing activity(ZPA)can specify the limb pattern along the anterior-posterior axis,The zone of polarizing activity(ZPA)in the posterior limb bud has organizing properties that are almost as striking as those of the Spemann organizer in amphibians,So

22、nic hedgehog(Shh)is expressed in the ZPA,Shh,Shh,Sonic hedgehog defines the signaling activity of the ZPA for development of the AP axis,The molecular basis for specification of ZPA,FGF8 in the AER induces the mesenchyme expressing the transcription factors Hoxb-8 and dHAND to express Shh,thereby fo

23、rming the ZPA in the posterior region of limb bud,Sonic hedgehog forms a morphogen gradient that specifies pattern along the limbs anterior-posterior axis,3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The ant

24、erior-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Development of the digits,Development of the vertebrate limb,The dorsal-ventral polarity of the limb bud is determined by the ectoderm encasing it,If the ectoderm is rotated 180 with respect t

25、o the limb bud mesenchyme,the dorsal-ventral axis is partially reversed.The Wnt7a gene is specifically expressed in the dorsal(but not ventral)ectoderm of chick and mouse limb buds,suggesting a role of Wnt7a in specifying dorsal-ventral polarity.,Loss of Wnt7a function leads to disruption of the dor

26、sal-ventral patterning of the limb,Vt:the ventral tendons（肌腱）,Vp:the ventral footpad（脚垫）,A:Wild type embryonic mouse forelimb pawB:The mice deficient for Wnt7a gene,The molecular mechanisms underlying the Wnt7a-mediated DV patterning of the limb,Wnt7a induces activation of the Lmx1 gene in the dorsa

27、l mesenchyme.Lmx1 gene encodes a transcription factor that appears to be essential for specifying dorsal cell fates in the limbSpatial expression of Wnt7a in the dorsal ectoderm is regulated by engrailed gene in the ventral ectoderm.,3 The limb development3.1 Specification and formation of the limb

28、bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The anterior-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Development of the digits,Development of the vertebrate limb,Molecular interactions that coordinate limb growth a

29、nd patterning along the three limb axes,3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 The anterior-posterior axial patterning 3.4 Patterning the dorsal-ventral axis 3.5 Coordinating the three axes 3.6 Develop

30、ment of the digits,Development of the vertebrate limb,The interdigital tissue specifies the identity of the digit forming anteriorly to the interdigital region in chick feet,The digital identity is regulated by BMP signaling in the interdigital region,Application of the BMP inhibitor Noggin to the i

31、nterdigital regions causes alterations in the digital identity similar to those observed when the interdigital region is removed,Separation of the digits is the result of programmed cell death,Regulation of the limb apoptosis by BMPs,Gremlin:an inhibitor of BMPs,Inhibition of cell death in the interdigital regions by blocking BMP signaling leads to the webbing of chick feet,