RT Journal Article
SR Electronic
T1 PDGF signaling directs cardiomyocyte movement toward the midline during heart tube assembly
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 076703
DO 10.1101/076703
A1 Joshua Bloomekatz
A1 Reena Singh
A1 Owen W.J. Prall
A1 Ariel C. Dunn
A1 Megan Vaughan
A1 Chin-San Loo
A1 Richard P. Harvey
A1 Deborah Yelon
YR 2016
UL http://biorxiv.org/content/early/2016/09/21/076703.abstract
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.