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A cellular atlas of
- Source :
- Development
- Publication Year :
- 2018
-
Abstract
- The Pitx2 gene encodes a homeobox transcription factor that is required for mammalian development. Disruption of PITX2 expression in humans causes congenital heart diseases and is associated with atrial fibrillation; however, the cellular and molecular processes dictated by Pitx2 during cardiac ontogeny remain unclear. To characterize the role of Pitx2 during murine heart development we sequenced over 75,000 single cardiac cell transcriptomes between two key developmental timepoints in control and Pitx2 null embryos. We found that cardiac cell composition was dramatically altered in mutants at both E10.5 and E13.5. Interestingly, the differentiation dynamics of both anterior and posterior second heart field-derived progenitor cells were disrupted in Pitx2 mutants. We also uncovered evidence for defects in left-right asymmetry within atrial cardiomyocyte populations. Furthermore, we were able to detail defects in cardiac outflow tract and valve development associated with Pitx2. Our findings offer insight into Pitx2 function and provide a compilation of gene expression signatures for further detailing the complexities of heart development that will serve as the foundation for future studies of cardiac morphogenesis, congenital heart disease and arrhythmogenesis.
- Subjects :
- Heart Defects, Congenital
Homeodomain Proteins
congenital, hereditary, and neonatal diseases and abnormalities
Sequence Analysis, RNA
Myocardium
Organogenesis
Gene Expression Regulation, Developmental
Nuclear Proteins
Heart
Heart Valves
stomatognathic diseases
Mice
stomatognathic system
Mutation
Animals
Myocytes, Cardiac
sense organs
Heart Atria
Transcriptome
Alleles
Transcription Factors
Research Article
Subjects
Details
- ISSN :
- 14779129
- Volume :
- 146
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Development (Cambridge, England)
- Accession number :
- edsair.pmid..........a8ca10dd11eb5cd3e16f5b5b69678821