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Title: The C. elegans SMOC-1 protein acts cell non-autonomously to promote bone morphogenetic protein signaling
Bone morphogenetic protein (BMP) signaling regulates many different developmental and homeostatic processes in metazoans. The BMP pathway is conserved in Caenorhabditis elegans, and is known to regulate body size and mesoderm development. We have identified the C. elegans smoc-1 (Secreted MOdular Calcium-binding protein-1) gene as a new player in the BMP pathway. smoc-1(0) mutants have a small body size, while overexpression of smoc-1 leads to a long body size and increased expression of the RAD-SMAD (reporter acting downstream of SMAD) BMP reporter, suggesting that SMOC-1 acts as a positive modulator of BMP signaling. Using double-mutant analysis, we showed that SMOC-1 antagonizes the function of the glypican LON-2 and acts through the BMP ligand DBL-1 to regulate BMP signaling. Moreover, SMOC-1 appears to specifically regulate BMP signaling without significant involvement in a TGFβ-like pathway that regulates dauer development. We found that smoc-1 is expressed in multiple tissues, including cells of the pharynx, intestine, and posterior hypodermis, and that the expression of smoc-1 in the intestine is positively regulated by BMP signaling. We further established that SMOC-1 functions cell nonautonomously to regulate body size. Human SMOC1 and SMOC2 can each partially rescue the smoc-1(0) mutant phenotype, suggesting that SMOC-1's function in modulating BMP signaling is evolutionarily conserved. Together, our findings highlight a conserved role of SMOC proteins in modulating BMP signaling in metazoans.  more » « less
Award ID(s):
1659534
NSF-PAR ID:
10093272
Author(s) / Creator(s):
Date Published:
Journal Name:
Genetics
Volume:
211
ISSN:
1943-2631
Page Range / eLocation ID:
683-702
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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