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

Hiroyuki Yamagishi, Eric N. Olson, Deepak Srivastava

Research output: Contribution to journalArticle

111 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalJournal of Clinical Investigation
Volume105
Issue number3
StatePublished - Feb 2000

Fingerprint

Basic Helix-Loop-Helix Transcription Factors
Blood Vessels
Endothelial Cells
Vascular Smooth Muscle
Smooth Muscle Myocytes
Neuropilin-1
Yolk Sac
Differentiation Antigens
Gene Deletion
Mesoderm
Vascular Endothelial Growth Factor A
Embryonic Development
Down-Regulation
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The basic helix-loop-helix transcription factor, dHAND, is required for vascular development. / Yamagishi, Hiroyuki; Olson, Eric N.; Srivastava, Deepak.

In: Journal of Clinical Investigation, Vol. 105, No. 3, 02.2000, p. 261-270.

Research output: Contribution to journalArticle

@article{6dbbd7d9225640eebdbcede4886644b2,
title = "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.",
author = "Hiroyuki Yamagishi and Olson, {Eric N.} and Deepak Srivastava",
year = "2000",
month = "2",
language = "English (US)",
volume = "105",
pages = "261--270",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",

}

TY - JOUR

T1 - The basic helix-loop-helix transcription factor, dHAND, is required for vascular development

AU - Yamagishi, Hiroyuki

AU - Olson, Eric N.

AU - Srivastava, Deepak

PY - 2000/2

Y1 - 2000/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033968447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033968447&partnerID=8YFLogxK

M3 - Article

C2 - 10675351

AN - SCOPUS:0033968447

VL - 105

SP - 261

EP - 270

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 3

ER -