PUBLICATION

Integrin α5 and Integrin α4 cooperate to promote endocardial differentiation and heart morphogenesis

Authors
Schumacher, J.A., Wright, Z.A., Owen, M., Bredemeier, N.O., Sumanas, S.
ID
ZDB-PUB-200708-11
Date
2020
Source
Developmental Biology   465(1): 46-57 (Journal)
Registered Authors
Sumanas, Saulius
Keywords
Cardiovascular, Endocardium, Integrin, Zebrafish
MeSH Terms
  • Animals
  • Cell Differentiation*
  • Endocardium/embryology*
  • Integrin alpha4/genetics
  • Integrin alpha4/metabolism*
  • Integrin alpha5/genetics
  • Integrin alpha5/metabolism*
  • Models, Biological*
  • Mutation
  • Organogenesis*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
32628938 Full text @ Dev. Biol.
Abstract
Endocardium is critically important for proper function of the cardiovascular system. Not only does endocardium connect the heart to blood vasculature, it also plays an important role in heart morphogenesis, valve formation, and ventricular trabeculation. The extracellular protein Fibronectin (Fn1) promotes endocardial differentiation, but the signaling pathways downstream of Fn1 that regulate endocardial development are not understood. Here, we analyzed the role of the Fibronectin receptors Integrin alpha5 (Itga5) and Integrin alpha4 (Itga4) in zebrafish heart development. We show that itga5 mRNA is expressed in both endocardium and myocardium during early stages of heart development. Through analysis of both itga5 single mutants and itga4;itga5 double mutants, we show that loss of both itga5 and itga4 results in enhanced defects in endocardial differentiation and morphogenesis compared to loss of itga5 alone. Loss of both itga5 and itga4 results in cardia bifida and severe myocardial morphology defects. Finally, we find that loss of itga5 and itga4 results in abnormally narrow anterior endodermal sheet morphology. Together, our results support a model in which Itga5 and Itga4 cooperate to promote endocardial differentiation, medial migration of endocardial and myocardial cells, and morphogenesis of anterior endoderm.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping