The basic helix-loop-helix transcription factor, dHAND, is required for vascular development
Hiroyuki Yamagishi, … , Eric N. Olson, Deepak Srivastava
Hiroyuki Yamagishi, … , Eric N. Olson, Deepak Srivastava
Published February 1, 2000
Citation Information: J Clin Invest. 2000;105(3):261-270. https://doi.org/10.1172/JCI8856.
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Article

The basic helix-loop-helix transcription factor, dHAND, is required for vascular development

Abstract

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 VEGF165 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.

Authors

Hiroyuki Yamagishi, Eric N. Olson, Deepak Srivastava

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Figure 1

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Expression of dHAND in the developing vasculature. Whole-mount in situ h...
Expression of dHAND in the developing vasculature. Whole-mount in situ hybridization revealed dHAND expression in the aortic arch arteries (aa) and aorta (ao) of an E10.0 embryo (a). Expression in the pharyngeal arches (pa), heart (ht), and limb bud (lb) was also seen. Sagittal section of an E9.5 embryo (b and c) showed expression in the aorta and aortic arch arteries. Sagittal section of an E10.5 embryo (d and e) demonstrated dHAND expression in the mesenchyme (m) of the third and fourth aortic arch arteries (arrowheads) and in the pharyngeal arch (pa) mesenchyme. b and d represent phase images of c and e, respectively. Expression of dHAND was also observed in the vascular smooth muscle cell line, A10, and in the adult heart and aorta by RT-PCR (f). RNA integrity was assayed by amplification of GAPDH. Yolk sac expression of dHAND was observed by RT-PCR in f and whole-mount in situ hybridization (arrowheads indicate vessels) (g). (h) Sense control.