The
highly conserved Wnt signalling pathway and its key mediator protein,
beta-catenin play essential roles during development and are required for adult
tissue homeostasis. Several studies have demonstrated that beta-catenin/Wnt
signalling is required for normal spermatogenesis, yet recent controversy has arisen
from reports showing differing results. In
some studies, the extent of Wnt activation appears to have been underestimated due
to the limited breadth of reporter techniques employed. Previous studies showed
that mice with up-regulated Wnt signalling in Sertoli cells exhibit disrupted
spermatogenesis, while mice with beta-catenin deletions under control of germ
cell- specific Cres identified variable phenotype severities. We documented several lines of evidence showing
that Wnt signalling is active in mitotic and post-mitotic germ cells of adult testes,
including: Wnt-reporter activity, observation of nuclear beta-catenin and expression
of Wnt downstream targets. These suggested
Wnt signalling may influence first proliferation, then differentiation, as
spermatogenesis progresses. We showed that Wnt signalling is essential for
normal spermatogenesis using AhCre
mouse models with testis-wide perturbations in beta-catenin and the negative regulator, Adenomatous Polyposis Coli [1]. We are
currently comparing mouse models in which beta-catenin is selectively deleted
in embryonic and early postnatal germ cells (VasaCre and Stra8Cre,
respectively) to delineate the importance of germ-cell intrinsic beta-catenin. We
are also assessing different beta-catenin mutant alleles to test the role of
beta-catenin in cell adhesion vs canonical Wnt signalling in vivo. Our data highlight
that factors such as breeding strategies, strain differences, and Cre
recombinase efficiency may influence phenotypic differences observed in Wnt
pathway mouse models. These analyses will
reveal how Wnt signalling activity in germ and somatic cells of the testis governs
normal spermatogenesis, and indicate how perturbations in Wnt signalling may contribute
to some cases of male infertility.