Open AccessPrecise spatial restriction of BMP signaling in developing joints is perturbed upon loss of embryo movement
Author(s) -
Pratik Singh,
Claire A. Shea,
Shashank Kumar Sonker,
Rebecca A. Rolfe,
Ayan Ray,
Sandeep Kumar,
Pankaj Gupta,
Paula Murphy,
Amitabha Bandyopadhyay
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.153460
Subject(s) - biology , wnt signaling pathway , microbiology and biotechnology , embryo , downregulation and upregulation , progenitor cell , signal transduction , synovial joint , bone morphogenetic protein , anatomy , genetics , gene , stem cell , pathology , medicine , articular cartilage , alternative medicine , osteoarthritis
Dynamic mechanical loading of synovial joints is necessary for normal joint development, as evidenced in certain clinical conditions, congenital disorders and animal models where dynamic muscle contractions are reduced or absent. Although the importance of mechanical forces on joint development is unequivocal, little is known about the molecular mechanisms involved. Here, using chick and mouse embryos, we observed that molecular changes in expression of multiple genes analyzed in the absence of mechanical stimulation are consistent across species. Our results suggest that abnormal joint development in immobilized embryos involves inappropriate regulation of Wnt and BMP signaling during definition of the emerging joint territories, i.e. reduced β-catenin activation and concomitant upregulation of pSMAD1/5/8 signaling. Moreover, dynamic mechanical loading of the developing knee joint activates Smurf1 expression; our data suggest that Smurf1 insulates the joint region from pSMAD1/5/8 signaling and is essential for maintenance of joint progenitor cell fate.