title: Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly.
abstract: 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. Mutation ofpdgfradisrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafishpdgframutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. Intriguingly, the ligandpdgfaais expressed in the endoderm medial to thepdgfra-expressing myocardial precursors. Ectopic expression ofpdgfaainterferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication can guide the cell movements that initiate cardiac morphogenesis.
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
authors.forename: Joshua
authors.identifier: 0000-0001-5816-2756
authors.initials: J
authors.lastname: Bloomekatz
authors.affiliation: Victor Chang Cardiac Research Institute, Darlinghurst, Australia.|St. Vincent's Clinical School, University of New South Wales, Kensington, Australia.
authors.forename: Reena
authors.identifier: 0000-0001-8860-8800
authors.initials: R
authors.lastname: Singh
authors.affiliation: Victor Chang Cardiac Research Institute, Darlinghurst, Australia.|Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Owen Wj
authors.identifier: 0000-0003-1600-5933
authors.initials: OW
authors.lastname: Prall
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
authors.forename: Ariel C
authors.identifier: 0000-0002-1715-3682
authors.initials: AC
authors.lastname: Dunn
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
authors.forename: Megan
authors.identifier: 0000-0002-8289-0638
authors.initials: M
authors.lastname: Vaughan
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
authors.forename: Chin-San
authors.identifier: 0000-0001-7915-2995
authors.initials: CS
authors.lastname: Loo
authors.affiliation: Victor Chang Cardiac Research Institute, Darlinghurst, Australia.|St. Vincent's Clinical School, University of New South Wales, Kensington, Australia.|School of Biotechnology and Biomolecular Science, University of New South Wales, Kensington, Australia.
authors.forename: Richard P
authors.identifier: 0000-0002-9950-9792
authors.initials: RP
authors.lastname: Harvey
authors.affiliation: Division of Biological Sciences, University of California, San Diego, La Jolla, United States.
authors.forename: Deborah
authors.identifier: 0000-0003-3523-4053
authors.initials: D
authors.lastname: Yelon
mesh_terms: D000818:Animals; D002465:Cell Movement; D055786:Gene Knockout Techniques; D006321:Heart / Q000196:embryology*; D051379:Mice; D009024:Morphogenesis; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059008:Time-Lapse Imaging; D015027:Zebrafish
chemical_list: D010982:Platelet-Derived Growth Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha
keywords: Pdgfra; cardia bifida; cardiac fusion; cardiac morphogenesis; developmental biology; endoderm; mouse; myocardium; stem cells; zebrafish