Progenitor expansion in apc mutants is mediated by Jak/Stat signaling

Abstract

Background: Mutations in APC, a negative regulator of the Wnt/-catenin pathway, can cause cancer as well as profound developmental defects. In both cases, affected cells adopt a proliferative progenitor state and fail to differentiate. While the upregulation of some target genes of Wnt/-catenin signaling has been shown to mediate these phenotypes in individual tissues, it is unclear whether a common mechanism underlies the defects in APC mutants. Results: Here we show that stat3, a known oncogene and a target of -catenin in multiple tissues, is upregulated in apc mutant zebrafish embryos. We further demonstrate that Jak/Stat signaling is necessary for the increased level of proliferation and neural progenitor gene expression observed in apc mutants. Conclusions: Together, our data suggest that the regulation of Jak/Stat signaling may represent a conserved mechanism explaining the expansion of undifferentiated cells downstream of APC mutations. © 2011 Lin et al; licensee BioMed Central Ltd.