Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly

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 endo...

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Main Authors: Joshua Bloomekatz, Reena Singh, Owen WJ Prall, Ariel C Dunn, Megan Vaughan, Chin-San Loo, Richard P Harvey, Deborah Yelon
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-01-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/21172
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author Joshua Bloomekatz
Reena Singh
Owen WJ Prall
Ariel C Dunn
Megan Vaughan
Chin-San Loo
Richard P Harvey
Deborah Yelon
author_facet Joshua Bloomekatz
Reena Singh
Owen WJ Prall
Ariel C Dunn
Megan Vaughan
Chin-San Loo
Richard P Harvey
Deborah Yelon
author_sort Joshua Bloomekatz
collection DOAJ
description 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 of pdgfra disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. 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 can guide the cell movements that initiate cardiac morphogenesis.
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spelling doaj.art-8610f2e05846412395a7cab115768ebe2022-12-22T02:02:00ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.21172Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assemblyJoshua Bloomekatz0https://orcid.org/0000-0001-5816-2756Reena Singh1https://orcid.org/0000-0001-8860-8800Owen WJ Prall2https://orcid.org/0000-0003-1600-5933Ariel C Dunn3https://orcid.org/0000-0002-1715-3682Megan Vaughan4https://orcid.org/0000-0002-8289-0638Chin-San Loo5https://orcid.org/0000-0001-7915-2995Richard P Harvey6https://orcid.org/0000-0002-9950-9792Deborah Yelon7https://orcid.org/0000-0003-3523-4053Division of Biological Sciences, University of California, San Diego, La Jolla, United StatesVictor Chang Cardiac Research Institute, Darlinghurst, Australia; St. Vincent’s Clinical School, University of New South Wales, Kensington, AustraliaVictor Chang Cardiac Research Institute, Darlinghurst, Australia; Peter MacCallum Cancer Centre, Melbourne, AustraliaDivision of Biological Sciences, University of California, San Diego, La Jolla, United StatesDivision of Biological Sciences, University of California, San Diego, La Jolla, United StatesDivision of Biological Sciences, University of California, San Diego, La Jolla, United StatesVictor 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, AustraliaDivision of Biological Sciences, University of California, San Diego, La Jolla, United StatesCommunication 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 of pdgfra disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. 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 can guide the cell movements that initiate cardiac morphogenesis.https://elifesciences.org/articles/21172cardiac morphogenesismyocardiumendodermPdgfracardiac fusioncardia bifida
spellingShingle Joshua Bloomekatz
Reena Singh
Owen WJ Prall
Ariel C Dunn
Megan Vaughan
Chin-San Loo
Richard P Harvey
Deborah Yelon
Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
eLife
cardiac morphogenesis
myocardium
endoderm
Pdgfra
cardiac fusion
cardia bifida
title Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
title_full Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
title_fullStr Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
title_full_unstemmed Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
title_short Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
title_sort platelet derived growth factor pdgf signaling directs cardiomyocyte movement toward the midline during heart tube assembly
topic cardiac morphogenesis
myocardium
endoderm
Pdgfra
cardiac fusion
cardia bifida
url https://elifesciences.org/articles/21172
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