A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo.

A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo.
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DOI:
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发表时间:
1999-03
期刊:
影响因子:
4.6
通讯作者:
T. Yamaguchi;A. Bradley;A. McMahon;Steven J. M. Jones
T. Yamaguchi;A. Bradley;A. McMahon;Steven J. M. Jones
中科院分区:
生物学2区
文献类型:
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作者:
T. Yamaguchi;A. Bradley;A. McMahon;Steven J. M. Jones

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形态发生依赖于对基本细胞过程如细胞增殖和分化的精确控制。Wnt 5a可以调节这些过程,因为它在原肠胚形成期间在生长胚胎的尾端以梯度表达,并且随后在从身体延伸的几个结构的最远端表达。Wnt 5a的功能丧失突变导致由于尾部结构的尺寸逐渐减小而不能延伸A-P轴。在四肢中,近端骨骼的截断和远端手指的缺失与进展区内推定的祖细胞增殖减少相关。然而,进展区标志物的表达,以及涉及远端生长和模式化的几个基因,包括Distalless,Hoxd和Fgf家族成员没有改变。结合在发育中的面部、耳朵和生殖器中观察到的生长缺陷,我们的数据表明Wnt 5a调节许多结构的共同途径,这些结构的发育需要从初级身体轴延伸。在进展区和原条中胚层中增殖细胞的数量减少表明Wnt 5a的一个功能是调节祖细胞的增殖。
Morphogenesis depends on the precise control of basic cellular processes such as cell proliferation and differentiation. Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during gastrulation, and later in the distal-most aspect of several structures that extend from the body. A loss-of-function mutation of Wnt5a leads to an inability to extend the A-P axis due to a progressive reduction in the size of caudal structures. In the limbs, truncation of the proximal skeleton and absence of distal digits correlates with reduced proliferation of putative progenitor cells within the progress zone. However, expression of progress zone markers, and several genes implicated in distal outgrowth and patterning including Distalless, Hoxd and Fgf family members was not altered. Taken together with the outgrowth defects observed in the developing face, ears and genitals, our data indicates that Wnt5a regulates a pathway common to many structures whose development requires extension from the primary body axis. The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells.