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XB-ART-45729
Dev Cell. August 14, 2012; 23 (2): 292-304.

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 .


Abstract
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: DK070858 NIDDK NIH HHS , K08 HL105661 NHLBI NIH HHS , K08 HL105661 NHLBI NIH HHS , K08 HL105661 NHLBI NIH HHS , K08 HL105661 NHLBI NIH HHS , K08 HL105661 NHLBI NIH HHS , K08 HL105661 NHLBI NIH HHS , P30 DK078392 NIDDK NIH HHS , R01 DK070858 NIDDK NIH HHS , T32 HD07463 NICHD NIH HHS

Genes referenced: bmp1 bmp2 bmp4 bmp7.1 casp3 chrd fbn1 fn1 frzb2 hhex nkx2-1 nr1h5 nr2e1 pdx1 smad1 szl tll1 tnni3 ventx1.2 ventx2.1
Antibodies referenced:
Morpholinos referenced:
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