Journal article
Myocardium and BMP signaling are required for endocardial differentiation
Development (Cambridge), Vol.142(13), pp.2304-2315
07/01/2015
DOI: 10.1242/dev.118687
PMCID: PMC4510589
PMID: 26092845
Abstract
Endocardial and myocardial progenitors originate in distinct regions of the anterior lateral plate mesoderm and migrate to the midline where they coalesce to form the cardiac tube. Endocardial progenitors acquire a molecular identity distinct from other vascular endothelial cells and initiate expression of specific genes such as nfatc1. Yet the molecular pathways and tissue interactions involved in establishing endocardial identity are poorly understood. The endocardium develops in tight association with cardiomyocytes. To test for a potential role of the myocardium in endocardial morphogenesis, we used two different zebrafish models deficient in cardiomyocytes: the hand2 mutant and a myocardial-specific genetic ablation method. We show that in hand2 mutants endocardial progenitors migrate to the midline but fail to assemble into a cardiac cone and do not express markers of differentiated endocardium. Endocardial differentiation defects were rescued by myocardial but not endocardial-specific expression of hand2. In metronidazole-treated myl7:nitroreductase embryos, myocardial cells were targeted for apoptosis, which resulted in the loss of endocardial nfatc1 expression. However, endocardial cells were present and retained expression of general vascular endothelial markers. We further identified bone morphogenetic protein (BMP) as a candidate myocardium-derived signal required for endocardial differentiation. Chemical and genetic inhibition of BMP signaling at the tailbud stage resulted in severe inhibition of endocardial differentiation while there was little effect on myocardial development. Heat-shock-induced bmp2b expression rescued endocardial nfatc1 expression in hand2 mutants and in myocardium-depleted embryos. Our results indicate that the myocardium is crucial for endocardial morphogenesis and differentiation, and identify BMP as a signal involved in endocardial differentiation.
Details
- Title: Subtitle
- Myocardium and BMP signaling are required for endocardial differentiation
- Creators
- Sharina Palencia-Desai - Cincinnati Children's Hospital Medical CenterMegan S Rost - Cincinnati Children's Hospital Medical CenterJennifer A Schumacher - Cincinnati Children's Hospital Medical CenterQuynh V Ton - Cincinnati Children's Hospital Medical CenterMichael P Craig - Cincinnati Children's Hospital Medical CenterKristina Baltrunaite - Cincinnati Children's Hospital Medical CenterAndrew L Koenig - Cincinnati Children's Hospital Medical CenterJinhu Wang - Duke Medical CenterKenneth D Poss - Duke Medical CenterNeil C Chi - University of California, San FranciscoDidier Y R Stainier - University of California, San FranciscoSaulius Sumanas - Cincinnati Children's Hospital Medical Center
- Resource Type
- Journal article
- Publication Details
- Development (Cambridge), Vol.142(13), pp.2304-2315
- DOI
- 10.1242/dev.118687
- PMID
- 26092845
- PMCID
- PMC4510589
- NLM abbreviation
- Development
- ISSN
- 0950-1991
- eISSN
- 1477-9129
- Grant note
- R01 HL054737 / NHLBI NIH HHS R01 HL107369 / NHLBI NIH HHS R01 HL081674 / NHLBI NIH HHS HL107369 / NHLBI NIH HHS HL081674 / NHLBI NIH HHS F32 HL124889 / NHLBI NIH HHS T32 HL125204 / NHLBI NIH HHS HL054737 / NHLBI NIH HHS
- Language
- English
- Date published
- 07/01/2015
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161457502771
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