Progenitor expansion in apc mutants is mediated by Jak/Stat signaling
- Authors
- Lin, J., Wang, X., and Dorsky, R.I.
- ID
- ZDB-PUB-111206-1
- Date
- 2011
- Source
- BMC Developmental Biology 11(1): 73 (Journal)
- Registered Authors
- Dorsky, Richard, Lin, Junji, Wang, Xu
- Keywords
- none
- MeSH Terms
-
- Wnt Signaling Pathway/genetics
- Transcriptional Activation
- Janus Kinases/genetics
- Janus Kinases/metabolism*
- Signal Transduction*
- Animals
- Neural Stem Cells/cytology
- Neural Stem Cells/metabolism
- Embryo, Nonmammalian/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Stem Cells/cytology*
- Stem Cells/metabolism
- Molecular Sequence Data
- STAT3 Transcription Factor/metabolism*
- Adenomatous Polyposis Coli Protein/genetics*
- Adenomatous Polyposis Coli Protein/metabolism
- Base Sequence
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 22136118 Full text @ BMC Dev. Biol.
Background
Mutations in APC, a negative regulator of the Wnt/beta-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/beta-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 beta-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.