{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:24:51Z","timestamp":1778851491751,"version":"3.51.4"},"reference-count":64,"publisher":"The Company of Biologists","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,2,15]]},"abstract":"<jats:p>A key process during vertebrate heart development is the migration of bilateral populations of myocardial precursors towards the midline to form the primitive heart tube. In zebrafish, signaling mediated by sphingosine-1-phosphate (S1P) and its cognate G protein-coupled receptor (S1pr2\/Mil) is essential for myocardial migration, but the underlying mechanisms remain undefined. Here, we show that suppression of G\u03b113 signaling disrupts myocardial migration, leading to the formation of two bilaterally located hearts (cardia bifida). Genetic studies indicate that G\u03b113 acts downstream of S1pr2 to regulate myocardial migration through a RhoGEF-dependent pathway. Furthermore, disrupting any component of the S1pr2\/G\u03b113\/RhoGEF pathway impairs endoderm convergence during segmentation, and the endodermal defects correlate with the extent of cardia bifida. Moreover, endoderm transplantation reveals that the presence of wild-type anterior endodermal cells in G\u03b113-deficient embryos is sufficient to rescue the endoderm convergence defect and cardia bifida, and, conversely, that the presence of anterior endodermal cells defective for S1pr2 or G\u03b113 in wild-type embryos causes such defects. Thus, S1pr2\/G\u03b113 signaling probably acts in the endoderm to regulate myocardial migration. In support of this notion, cardiac-specific expression of G\u03b113 fails to rescue cardia bifida in the context of global G\u03b113 inhibition. Our data demonstrate for the first time that the G\u03b113\/RhoGEF-dependent pathway functions downstream of S1pr2 to regulate convergent movement of the endoderm, an event that is crucial for coordinating myocardial migration.<\/jats:p>","DOI":"10.1242\/dev.085340","type":"journal-article","created":{"date-parts":[[2013,1,15]],"date-time":"2013-01-15T03:24:15Z","timestamp":1358220255000},"page":"789-799","source":"Crossref","is-referenced-by-count":52,"title":["S1pr2\/G\u03b113 signaling controls myocardial migration by regulating endoderm convergence"],"prefix":"10.1242","volume":"140","author":[{"given":"Ding","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Carver College of Medicine, the University of Iowa, 1-400 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242-1109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Carver College of Medicine, the University of Iowa, 1-400 Bowen Science Building, 51 Newton Road, Iowa City, IA 52242-1109, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2021042622170652000_R1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1006\/dbio.1999.9441","article-title":"casanova plays an early and essential role in endoderm formation in zebrafish","volume":"215","author":"Alexander","year":"1999","journal-title":"Dev. 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