Document Detail


Sizzled-tolloid interactions maintain foregut progenitors by regulating fibronectin-dependent BMP signaling.
MedLine Citation:
PMID:  22863744     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Alan P Kenny; Scott A Rankin; Andrew W Allbee; Allison R Prewitt; Zheng Zhang; Meredith E Tabangin; Emily T Shifley; Mariana P Louza; Aaron M Zorn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2012-08-02
Journal Detail:
Title:  Developmental cell     Volume:  23     ISSN:  1878-1551     ISO Abbreviation:  Dev. Cell     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-17     Completed Date:  2012-11-01     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  101120028     Medline TA:  Dev Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  292-304     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Perinatal Institute, Cincinnati Children's Research Foundation, Cincinnati, OH 45229, USA. alan.kenny@cchmc.org
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE38654
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Morphogenetic Proteins / metabolism
Cell Lineage
Embryo, Mammalian / metabolism
Fibronectins / metabolism*
Gene Expression Regulation, Developmental
Intestines / embryology,  metabolism*
Protein Binding
Signal Transduction*
Stem Cells / cytology,  metabolism*
Tolloid-Like Metalloproteinases / genetics,  metabolism*
Xenopus Proteins / genetics,  metabolism*
Xenopus laevis / embryology,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
DK070858/DK/NIDDK NIH HHS; K08 HL105661/HL/NHLBI NIH HHS; K08 HL105661/HL/NHLBI NIH HHS; P30 DK078392/DK/NIDDK NIH HHS; R01 DK070858/DK/NIDDK NIH HHS; T32 HD07463/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Fibronectins; 0/Xenopus Proteins; 0/sizzled protein, Xenopus; EC 3.4.-/Tolloid-Like Metalloproteinases; EC 3.4.24.-/tll1 protein, Xenopus
Comments/Corrections

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