The basic helix-loop-helix transcription factor, dHAND, is required for vascular development.
Reciprocal interactions between vascular endothelial cells and vascular mesenchymal cells are essential for angiogenesis. Here we show that the basic helix-loop-helix transcription factor, dHAND/Hand2, is expressed in the developing vascular mesenchyme and its derivative, vascular smooth muscle cells (VSMCs). Targeted deletion of the dHAND gene in mice revealed severe defects of embryonic and yolk sac vascular development by embryonic day 9.5. Vascular endothelial cells expressed most markers of differentiation. Vascular mesenchymal cells migrated appropriately but failed to make contact with vascular endothelial cells and did not differentiate into VSMCs. In a screen for genes whose expression was dependent upon dHAND (using subtractive hybridization comparing wild-type and dHAND-null hearts), the VEGF(165) receptor, neuropilin-1, was found to be downregulated in dHAND mutants. These results suggest that dHAND is required for vascular development and regulates angiogenesis, possibly through a VEGF signaling pathway.
Yamagishi
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Department of Pediatrics, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Olson
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Srivastava
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D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001808:Blood Vessels / Q000196:embryology* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C498766:Hand2 protein, mouse; C410915:hand2 protein, zebrafish