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Early exclusion of hand1-deficient cells from distinct regions of the left ventricular myocardium in chimeric mouse embryos.
- Source :
-
Developmental biology [Dev Biol] 2000 Nov 01; Vol. 227 (1), pp. 156-68. - Publication Year :
- 2000
-
Abstract
- The basic helix-loop-helix transcription factor gene Hand1 has been implicated in development of the heart. However, the early lethality of Hand1-null mutant mouse embryos has precluded a precise understanding of its function. In this study, we have generated Hand1 homozygous mutant ES cells and performed in vitro differentiation experiments and chimeric analysis to study the role of Hand1 function during cardiac development. Hand1-null ES cells were able to differentiate into beating cardiomyocytes in vitro that expressed cardiac myosin and several cardiac-specific transcripts including Nkx2-5, alpha-cardiac actin, and the myofilament genes myosin light chain 2a and 2v. In chimeras derived from Hand1-null ES cells and ROSA26 embryos, mutant cells were underrepresented in the left caudal region of the linear heart tube at E8.0. By E9.5, after cardiac looping, mutant cells were underrepresented in the anterior region of the outer curvature of the left ventricular myocardium, but did contribute to other parts of the left ventricle and to other cardiac chambers. These results imply that Hand1 is not essential for differentiation of ventricular cardiomyocytes. Hand1-null cells were also underrepresented in several other regions of later embryos, including the rhombencephalic neural tube that was associated with a deficiency of mutant cells in the neural crest cell-derived cardiac outflow tract and first branchial arch. In summary, Hand1 has cell-autonomous functions during cardiac morphogenesis in both mesodermal and neural crest derivatives.<br /> (Copyright 2000 Academic Press.)
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation
Cell Movement
Chimera metabolism
DNA-Binding Proteins genetics
Gene Deletion
Genes, Reporter
Heart Ventricles abnormalities
Heart Ventricles pathology
Immunohistochemistry
In Situ Hybridization
Mesoderm cytology
Mesoderm metabolism
Mice
Mice, Transgenic
Morphogenesis
Myocardium metabolism
Neural Crest cytology
Neural Crest metabolism
RNA, Messenger genetics
RNA, Messenger metabolism
Stem Cells cytology
Stem Cells metabolism
Transcription Factors genetics
Chimera embryology
DNA-Binding Proteins deficiency
DNA-Binding Proteins physiology
Heart Ventricles cytology
Heart Ventricles embryology
Myocardium cytology
Transcription Factors deficiency
Transcription Factors physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0012-1606
- Volume :
- 227
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 11076684
- Full Text :
- https://doi.org/10.1006/dbio.2000.9864