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Dev Cell 2012 Aug 14;232:292-304. doi: 10.1016/j.devcel.2012.07.002.
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Sizzled-tolloid interactions maintain foregut progenitors by regulating fibronectin-dependent BMP signaling.

Kenny AP , Rankin SA , Allbee AW , Prewitt AR , Zhang Z , Tabangin ME , Shifley ET , Louza MP , Zorn AM .

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 (Szl) and the extracellular metalloprotease Tolloid-like 1 (Tll1). Szl negatively regulates Tll activity to control deposition of a fibronectin (FN) matrix between the mesoderm and endoderm, which is required to maintain BMP signaling. Foregut-specific Szl 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.

PubMed ID: 22863744
PMC ID: PMC3615545
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bmp1 bmp2 bmp4 bmp7.1 chrd fbn1 fn1 frzb2 hhex nr1h5 nr2e1 pdx1 smad1 szl tll1 ventx2
Morpholinos: bmp1 MO1 bmp2 MO1 fn1 MO1 fn1 MO2 szl MO1 tll1 MO1

GEO Series: GSE38654: NCBI
Phenotypes: Xla Wt + Caspase Inhibitor I (fig.3.c) [+]

Article Images: [+] show captions
References [+] :
Blitz, Is chordin a long-range- or short-range-acting factor? Roles for BMP1-related metalloproteases in chordin and BMP4 autofeedback loop regulation. 2000, Pubmed, Xenbase