PT  - JOURNAL ARTICLE
AU  - Joshua Bloomekatz
AU  - Reena Singh
AU  - Owen W.J. Prall
AU  - Ariel C. Dunn
AU  - Megan Vaughan
AU  - Chin-San Loo
AU  - Richard P. Harvey
AU  - Deborah Yelon
TI  - PDGF signaling directs cardiomyocyte movement toward the midline during heart tube assembly
AID  - 10.1101/076703
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 076703
4099  - http://biorxiv.org/content/early/2016/09/21/076703.short
4100  - http://biorxiv.org/content/early/2016/09/21/076703.full
AB  - Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. In both zebrafish and mouse, mutation of pdgfra inhibits cardiac fusion and can lead to cardia bifida. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication guides the cell movements that initiate cardiac morphogenesis.IMPACT STATEMENT Studies in zebrafish and mouse implicate the PDGF signaling pathway in the communication between the endoderm and the myocardium that drives medial myocardial movement and thereby initiates cardiac morphogenesis.