Cardiovascular development and survival require Mef2c function in the myocardial but not the endothelial lineage
| Autor: | Brian L. Black, Stefan C. Materna, Kelly Lammerts van Bueren, Tanvi Sinha, Ralston M. Barnes |
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| Rok vydání: | 2018 |
| Předmět: |
Male
Mouse Endothelial cells Organogenesis Cardiovascular Medical and Health Sciences Cardiovascular System Transgenic Heart development Congenital Mice 0302 clinical medicine Pregnancy Conditional gene knockout Morphogenesis 2.1 Biological and endogenous factors Developmental Vascular remodeling MEF2C Aetiology Heart Defects Mice Knockout 0303 health sciences MEF2 Transcription Factors Gene Expression Regulation Developmental Heart Biological Sciences Phenotype Cell biology Mutant Strains Heart Disease medicine.anatomical_structure Knockout mouse Stem Cell Research - Nonembryonic - Non-Human Female Mef2 Heart Defects Congenital Endothelium Knockout Mice Transgenic Biology Article Cardiovascular Physiological Phenomena 03 medical and health sciences Vascular Genetics medicine Animals Molecular Biology 030304 developmental biology Vascular development Cell Biology Stem Cell Research Embryonic stem cell Mice Mutant Strains Gene Expression Regulation Endothelium Vascular 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental biology, vol 445, iss 2 |
| ISSN: | 1095-564X |
| Popis: | MEF2C is a member of the highly conserved MEF2 family of transcription factors and is a key regulator of cardiovascular development. In mice, Mef2c is expressed in the developing heart and vasculature, including the endothelium. Loss of Mef2c function in germline knockout mice leads to early embryonic demise and profound developmental abnormalities in the cardiovascular system. Previous attempts to uncover the cause of embryonic lethality by specifically disrupting Mef2c function in the heart or vasculature failed to recapitulate the global Mef2c knockout phenotype and instead resulted in relatively minor defects that did not compromise viability or result in significant cardiovascular defects. However, previous studies examined the requirement of Mef2c in the myocardial and endothelial lineages using Cre lines that begin to be expressed after the expression of Mef2c has already commenced. Here, we tested the requirement of Mef2c in the myocardial and endothelial lineages using conditional knockout approaches in mice with Cre lines that deleted Mef2c prior to onset of its expression in embryonic development. We found that deletion of Mef2c in the early myocardial lineage using Nkx2–5(Cre) resulted in cardiac and vascular abnormalities that were indistinguishable from the defects in the global Mef2c knockout. In contrast, early deletion of Mef2c in the vascular endothelium using an Etv2::Cre line active prior to the onset of Mef2c expression resulted in viable offspring that were indistinguishable from wild type controls with no overt defects in vascular development, despite nearly complete early deletion of Mef2c in the vascular endothelium. Thus, these studies support the idea that the requirement of MEF2C for vascular development is secondary to its requirement in the heart and suggest that the observed failure in vascular remodeling in Mef2c knockout mice results from defective heart function. |
| Databáze: | OpenAIRE |
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