Targeted deletion of Hand2 in cardiac neural crest-derived cells influences cardiac gene expression and outflow tract development
| Autor: | Sophia E. Troy, Marthe J. Howard, Kristen L. Holler, Joshua W. Vincentz, Anthony B. Firulli, Tyler J. Hendershot |
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| Rok vydání: | 2010 |
| Předmět: |
Transcriptional Activation
animal structures Cellular differentiation Gene Dosage Connexins Article Bulbus cordis Mice Hand2(dHand) bHLH Cell type-specific gene regulation Genetic model Basic Helix-Loop-Helix Transcription Factors Animals Outflow tract Gene microarray Promoter Regions Genetic Molecular Biology Regulation of gene expression biology Heart development Cardiac cushion Cell Cycle Gene Expression Regulation Developmental Neural crest Heart Cell Biology Molecular biology Outflow tract morphogenesis Cell biology Neural Crest embryonic structures cardiovascular system biology.protein HAND2 Developmental Biology |
| Zdroj: | Developmental Biology. 341:291-304 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2010.02.001 |
| Popis: | The basic helix–loop–helix DNA binding protein Hand2 has critical functions in cardiac development both in neural crest-derived and mesoderm-derived structures. Targeted deletion of Hand2 in the neural crest has allowed us to genetically dissect Hand2-dependent defects specifically in outflow tract and cardiac cushion independent of Hand2 functions in mesoderm-derived structures. Targeted deletion of Hand2 in the neural crest results in misalignment of the aortic arch arteries and outflow tract, contributing to development of double outlet right ventricle (DORV) and ventricular septal defects (VSD). These neural crest-derived developmental anomalies are associated with altered expression of Hand2-target genes we have identified by gene profiling. A number of Hand2 direct target genes have been identified using ChIP and ChIP-on-chip analyses. We have identified and validated a number of genes related to cell migration, proliferation/cell cycle and intracellular signaling whose expression is affected by Hand2 deletion in the neural crest and which are associated with development of VSD and DORV. Our data suggest that Hand2 is a multifunctional DNA binding protein affecting expression of target genes associated with a number of functional interactions in neural crest-derived cells required for proper patterning of the outflow tract, generation of the appropriate number of neural crest-derived cells for elongation of the conotruncus and cardiac cushion organization. Our genetic model has made it possible to investigate the molecular genetics of neural crest contributions to outflow tract morphogenesis and cell differentiation. |
| Databáze: | OpenAIRE |
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