Journal
DEVELOPMENTAL CELL
Volume 23, Issue 2, Pages 292-304Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2012.07.002
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Funding
- CCHMC Procter Scholarship
- PHS [P30 DK078392, DK070858]
- [K08 HL105661]
- [T32 HD07463]
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The liver, pancreas, and lungs are induced from endoderm progenitors by a series of dynamic growth factor signals from the mesoderm, but how the temporal-spatial activity of these signals is controlled is poorly understood. We have identified an extracellular regulatory loop required for robust bone morphogenetic protein (BMP) signaling in the Xenopus foregut. We show that BMP signaling is required to maintain foregut progenitors and induce expression of the secreted frizzled related protein Sizzled (SzI) and the extracellular metalloprotease Tolloid-like 1 (TII1). SzI negatively regulates TII activity to control deposition of a fibronectin (FN) matrix between the mesoderm and endoderm, which is required to maintain BMP signaling. Foregut-specific SzI depletion results in a loss of the FN matrix and failure to maintain robust pSmad1 levels, causing a loss of foregut gene expression and organ agenesis. These results have implications for BMP signaling in diverse contexts and the differentiation of foregut tissue from stem cells.
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