Understanding limb development not only gives insights into the outgrowth and differentiation of the limb,but also has clinical relevance.Limb development begins with two paired limb buds(forelimb and hindlimb buds),w...Understanding limb development not only gives insights into the outgrowth and differentiation of the limb,but also has clinical relevance.Limb development begins with two paired limb buds(forelimb and hindlimb buds),which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm,termed the apical ectodermal ridge(AER).As a transitional embryonic structure,the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres,feedback loops,and other cell ac-tivities by secretory signalling and the activation of gene expression.Within the scope of proximodistal pattering,it is understood that while fibroblast growth factors(FGFs)function sequentially over time as primary components of the AER signalling process,there is still no consensus on models that would explain proximodistal patterning itself.In anteroposterior pattermning,the AER has a dual-direction regulation by which it promotes the sonic hedgehog(Shh)gene expression in the zone of polarizing activity(ZPA)for proliferation,and inhibits Shh expression in the anterior mesenchyme.In dorsoventral patterming,the AER activates Engrailed-1(En1)expression,and thus represses Wnt family member 7a(Wnt7a)expression in the ventral ectoderm by the expression of Fgfs,Sp6/8,and bone morpho-genetic protein(Bmp)genes.The AER also plays a vital role in shaping the individual digits,since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis.In summary,the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern fomation,as the development of its areas proceeds simultaneously.展开更多
基金Key Research and Development Project of Shandong Province(No.2017G006043),China。
文摘Understanding limb development not only gives insights into the outgrowth and differentiation of the limb,but also has clinical relevance.Limb development begins with two paired limb buds(forelimb and hindlimb buds),which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm,termed the apical ectodermal ridge(AER).As a transitional embryonic structure,the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres,feedback loops,and other cell ac-tivities by secretory signalling and the activation of gene expression.Within the scope of proximodistal pattering,it is understood that while fibroblast growth factors(FGFs)function sequentially over time as primary components of the AER signalling process,there is still no consensus on models that would explain proximodistal patterning itself.In anteroposterior pattermning,the AER has a dual-direction regulation by which it promotes the sonic hedgehog(Shh)gene expression in the zone of polarizing activity(ZPA)for proliferation,and inhibits Shh expression in the anterior mesenchyme.In dorsoventral patterming,the AER activates Engrailed-1(En1)expression,and thus represses Wnt family member 7a(Wnt7a)expression in the ventral ectoderm by the expression of Fgfs,Sp6/8,and bone morpho-genetic protein(Bmp)genes.The AER also plays a vital role in shaping the individual digits,since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis.In summary,the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern fomation,as the development of its areas proceeds simultaneously.
