title: Smarcd3b and Gata5 promote a cardiac progenitor fate in the zebrafish embryo.
abstract: Development of the heart requires recruitment of cardiovascular progenitor cells (CPCs) to the future heart-forming region. CPCs are the building blocks of the heart, and have the potential to form all the major cardiac lineages. However, little is known regarding what regulates CPC fate and behavior. Activity of GATA4, SMARCD3 and TBX5 - the `cardiac BAF' (cBAF) complex, can promote myocardial differentiation in embryonic mouse mesoderm. Here, we exploit the advantages of the zebrafish embryo to gain mechanistic understanding of cBAF activity. Overexpression of smarcd3b and gata5 in zebrafish results in an enlarged heart, whereas combinatorial loss of cBAF components inhibits cardiac differentiation. In transplantation experiments, cBAF acts cell autonomously to promote cardiac fate. Remarkably, cells overexpressing cBAF migrate to the developing heart and differentiate as cardiomyocytes, endocardium and smooth muscle. This is observed even in host embryos that lack endoderm or cardiac mesoderm. Our results reveal an evolutionarily conserved role for cBAF activity in cardiac differentiation. Importantly, they demonstrate that Smarcd3b and Gata5 can induce a primitive, CPC-like state.
authors.affiliation: Program in Development and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Lou
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Deshwar
authors.forename: J Gage
authors.initials: JG
authors.lastname: Crump
authors.forename: Ian C
authors.initials: IC
authors.lastname: Scott
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000378:metabolism; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism; D050992:GATA5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D050980:GATA Transcription Factors; D050992:GATA5 Transcription Factor; C525957:Gata4 protein, zebrafish; C561114:SMARCD3B protein, zebrafish; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D014157:Transcription Factors; D029961:Zebrafish Proteins; C494754:gata5 protein, zebrafish; D005346:Fibroblast Growth Factors