Requirement for Wnt3 in vertebrate axis formation

Abstract

Several studies have implicated Wnt signalling in primary axis formation during vertebrate embryogenesis, yet no Wnt protein has been shown to be essential for this process. In the mouse, primitive streak formation is the first overt morphological sign of the anterior-posterior axis. Here we show that Wnt3 is expressed before gastrulation in the proximal epiblast of the egg cylinder, then is restricted to the posterior proximal epiblast and its associated visceral endoderm and subsequently to the primitive streak and mesoderm. Wnt3-/- mice develop a normal egg cylinder but do not form a primitive streak, mesoderm or node. The epiblast continues to proliferate in an undifferentiated state that lacks anterior-posterior neural patterning, but anterior visceral endoderm markers are expressed and correctly positioned. Our results suggest that regional patterning of the visceral endoderm is independent of primitive streak formation, but the subsequent establishment of anterior-posterior neural pattern in the ectoderm is dependent on derivatives of the primitive streak. These studies provide genetic proof for the requirement of Wnt3 in primary axis formation in the mouse.

Expression of all Wnt genes and their secreted antagonists during mouse blastocyst and postimplantation development

“…It is, however, turned off in mesoderm migrating away from the primitive streak (data not shown and Zakin et al, 1998). This expression pattern is similar to the expression pattern of Wnt3, which is required for gastrulation, and it suggests that Wnt2b may play an important role in gastrulation (Liu et al, 1999). Wnt2b and Wnt3 may also be partially redundant because their expression domains are largely overlapping.…”

“…According to the expression profile, the expression of Wnt3 is highest at gastrulation as shown by in situ hybridization (Liu et al, 1999). No clear localized expression of Wnt6 could be detected at the examined postimplantation stages by in situ hybridization (data not shown).…”

“…It was shown that Wnt3 mutant embryos lack a primitive streak; therefore, no mesoderm is formed during gastrulation (Liu et al, 1999). The anterior visceral endoderm (aVE), a cell layer underlying the future head region and located in the embryo on the side opposite to the primitive streak, however, is properly located and correctly patterned.…”

“…Wnt2b and Wnt3 may also be partially redundant because their expression domains are largely overlapping. Indeed, Wnt2b has been shown to trigger the canonical Wnt pathway and could eventually be responsible for part of the phenotype of the beta-Catenin mutant embryo (lack of anterior migration of the distal visceral endoderm at 5.5 dpc) that is not mimicked in the Wnt3 mutant (Liu et al, 1999;Huelsken et al, 2000;Kubo et al, 2003).…”

Molecular basis for skeletal variation: insights from developmental genetic studies in mice

“…The end result is a truncation of the body axis at the level of the forelimbs (Augustine et al, 1993;Takada et al, 1994). In Wnt3 mutants, the primitive streak does not even form, and the node, as well as the mesoderm, is strikingly absent (Liu et al, 1999). Fgf genes are expressed in complex, partially overlapping patterns during embryogenesis.…”