Progenitor expansion in apc mutants is mediated by Jak/Stat signaling
Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, UT 84132, USA
BMC Developmental Biology 2011, 11:73 doi:10.1186/1471-213X-11-73Published: 2 December 2011
Mutations in APC, a negative regulator of the Wnt/ß-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/ß-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.
Here we show that stat3, a known oncogene and a target of ß-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.
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.