Yamaguchi T P, Bradley A, McMahon A P, Jones S
Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, Cambridge, MA 02138, USA.
Development. 1999 Mar;126(6):1211-23. doi: 10.1242/dev.126.6.1211.
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.
形态发生取决于对基本细胞过程的精确控制，如细胞增殖和分化。Wnt5a可能调节这些过程，因为它在原肠胚形成期间在生长胚胎的尾端以梯度形式表达，并且后来在从身体延伸的几个结构的最远端表达。Wnt5a的功能丧失突变导致无法延长前后轴，这是由于尾部结构的大小逐渐减小。在四肢中，近端骨骼的截断和远端指骨的缺失与进展区假定祖细胞增殖的减少相关。然而，进展区标记物以及包括Distalless、Hoxd和Fgf家族成员在内的一些与远端生长和模式形成相关的基因的表达并未改变。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Wnt5a调节许多结构共有的一条途径，这些结构的发育需要从原始体轴延伸。进展区和原条中胚层中增殖细胞数量的减少表明Wnt5a的一个功能是调节祖细胞的增殖。
