A <i>Wnt5a</i> pathway underlies outgrowth of multiple structures in the vertebrate embryo

TLDR

Morphogenesis relies on precise regulation of cell proliferation and differentiation, and Wnt5a is a candidate regulator expressed in gradients during gastrulation and in distal aspects of extending structures. Loss of Wnt5a function impairs axial and limb outgrowth by reducing progenitor proliferation in the progress zone and primitive streak, causing a truncated A‑P axis, shortened proximal skeleton, and missing distal digits, while leaving patterning gene expression unchanged, indicating Wnt5a drives a common outgrowth pathway.

Abstract

ABSTRACT 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.