VI-胚层发育与器官系统发生(II)课件

《VI-胚层发育与器官系统发生(II)课件》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)课件（43页珍藏版）》请在装配图网上搜索。

1、Developmental BiologyChapter 6:Organogenesis development of the vertebrate limbThe embryonic chick wingThe vertebrate limb develops from a limb bud3 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-po

2、sterior 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 limb3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axis3.3 Th

3、e 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 limbThe vertebrate limb develops from a limb budProliferation of mesodermal cells from the lateral plate mesoderm causes the limb b

4、ud to bulge outwardWhile the lateral plate mesodermal cells generate the skeletal elements of the limb,cells from the somites provide the limbs musculatureFGF10 secreted from the lateral plate mesoderm cells is the signal for limb bud inductionA:FGF10 becomes expressed in the lateral plate mesoderm

5、of the limb bud-forming regionB:Ectopic expression of FGF10 beneath the flank ectoderm induces extra limbFGF10Ectopic limbFGF10 initiates the limb bud-forming interactions between the ectoderm and the mesoderm via dual signaling inductionA:FGF10 is originally expressed throughout the lateral plate m

6、esodermB:FGF10 becomes restricted to the limb bud-forming regions,controlled by Wnt 2b and Wnt 8c respectivelyC:Dual induction between FGF10 in the mesoderm 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 gestation3

7、 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 ver

8、tebrate limbApical ectodermal ridge(AER)Progress zone(PZ)The AER is required for both the outgrowth of limb and the correct proximo-distal patterningFGF8 is expressed in the apical ectodermal ridge(AER)FGF8 can functionally substitute for the AERThe similar results can be obtained with FGF4,indicati

9、ng 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 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 limbThe proxima

10、l-distal growth of the limb bud involves interactions between the AER and the underlying mesenchyme n Role of the AER or the PZ(progress zone)in specifying the proximal-distal axis?n The mechamisms underlying the PD axis specification and patterning?How is development of the proximal-distal axis acc

11、omplished during the limb outgrowth?Specification of proximal-distal axis is controlled by the progress zone mesenchyme,rather the AER(I)A.Older AER combined with younger mesoderm generates normal limbs,rather producing limbs with deletions in the middle.B.Younger AER combined with older mesoderm ge

12、nerates normal limbs,rather producing duplications of structures.The following two transplantation experiments did not support the notion that the AER specifies the proxiomal-distal axis of the developing limbs.A.An early wing-bud progress zone was transplanted to a late wing bud that had alrealy fo

13、rmed ulna and radiusB.A late wing-bud progress zone was transplanted to an early wing budExtra proximal structureLack of intermediate structuresSpecification of proximal-distal axis is controlled by the progress zone mesenchyme,rather the AER(II)Two proposed models for the mesodermal specification o

14、f 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 in early budHox 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

15、to lacking the ulna and radius of the forelimbs Human synpolydactyly(many fingers joined together)syndrome results from homozygosity for a mutation at the Hoxd-13 loci3 The limb development3.1 Specification and formation of the limb bud3.2 The limb outgrowth and generation of the proximal-distal axi

16、s3.3 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 limbZone of polarizing activity(ZPA)can specify the limb pattern along the anterior-posterior axisThe zone of polarizing act

17、ivity(ZPA)in the posterior limb bud has organizing properties that are almost as striking as those of the Spemann organizer in amphibiansSonic hedgehog(Shh)is expressed in the ZPAShhShhSonic hedgehog defines the signaling activity of the ZPA for development of the AP axisThe molecular basis for spec

18、ification of ZPAFGF8 in the AER induces the mesenchyme expressing the transcription factors Hoxb-8 and dHAND to express Shh,thereby forming the ZPA in the posterior region of limb budSonic hedgehog forms a morphogen gradient that specifies pattern along the limbs anterior-posterior axis3 The limb de

19、velopment3.1 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 limb

20、The dorsal-ventral polarity of the limb bud is determined by the ectoderm encasing itn If the ectoderm is rotated 180 with respect to the limb bud mesenchyme,the dorsal-ventral axis is partially reversed.n The Wnt7a gene is specifically expressed in the dorsal(but not ventral)ectoderm of chick and m

21、ouse limb buds,suggesting a role of Wnt7a in specifying dorsal-ventral polarity.Loss of Wnt7a function leads to disruption of the dorsal-ventral patterning of the limbVt:the ventral tendons（肌腱肌腱）Vp:the ventral footpad（脚垫脚垫）A:Wild type embryonic mouse forelimb pawB:The mice deficient for Wnt7a geneTh

22、e molecular mechanisms underlying the Wnt7a-mediated DV patterning of the limbWnt7a induces activation of the Lmx1 gene in the dorsal 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

23、 ectoderm is regulated by engrailed gene in the ventral ectoderm.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 t

24、he three axes 3.6 Development of the digits Development of the vertebrate limbMolecular interactions that coordinate limb growth and 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

25、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 limbThe interdigital tissue specifies the identity of the digit forming anteriorly to the interdigital region in chick fe

26、etThe digital identity is regulated by BMP signaling in the interdigital regionApplication of the BMP inhibitor Noggin to the interdigital regions causes alterations in the digital identity similar to those observed when the interdigital region is removedSeparation of the digits is the result of programmed cell deathRegulation of the limb apoptosis by BMPsGremlin:an inhibitor of BMPsInhibition of cell death in the interdigital regions by blocking BMP signaling leads to the webbing of chick feet