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Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts.

Publication ,  Journal Article
Lyden, D; Young, AZ; Zagzag, D; Yan, W; Gerald, W; O'Reilly, R; Bader, BL; Hynes, RO; Zhuang, Y; Manova, K; Benezra, R
Published in: Nature
October 14, 1999

Id proteins may control cell differentiation by interfering with DNA binding of transcription factors. Here we show that targeted disruption of the dominant negative helix-loop-helix proteins Id1 and Id3 in mice results in premature withdrawal of neuroblasts from the cell cycle and expression of neural-specific differentiation markers. The Id1-Id3 double knockout mice also display vascular malformations in the forebrain and an absence of branching and sprouting of blood vessels into the neuroectoderm. As angiogenesis both in the brain and in tumours requires invasion of avascular tissue by endothelial cells, we examined the Id knockout mice for their ability to support the growth of tumour xenografts. Three different tumours failed to grow and/or metastasize in Id1+/- Id3-/- mice, and any tumour growth present showed poor vascularization and extensive necrosis. Thus, the Id genes are required to maintain the timing of neuronal differentiation in the embryo and invasiveness of the vasculature. Because the Id genes are expressed at very low levels in adults, they make attractive new targets for anti-angiogenic drug design.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

October 14, 1999

Volume

401

Issue

6754

Start / End Page

670 / 677

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Transcription Factors
  • Repressor Proteins
  • Neurons
  • Nerve Tissue Proteins
  • Neovascularization, Physiologic
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Mutation
 

Citation

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Lyden, D., Young, A. Z., Zagzag, D., Yan, W., Gerald, W., O’Reilly, R., … Benezra, R. (1999). Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature, 401(6754), 670–677. https://doi.org/10.1038/44334
Lyden, D., A. Z. Young, D. Zagzag, W. Yan, W. Gerald, R. O’Reilly, B. L. Bader, et al. “Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts.Nature 401, no. 6754 (October 14, 1999): 670–77. https://doi.org/10.1038/44334.
Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O’Reilly R, et al. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature. 1999 Oct 14;401(6754):670–7.
Lyden, D., et al. “Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts.Nature, vol. 401, no. 6754, Oct. 1999, pp. 670–77. Pubmed, doi:10.1038/44334.
Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O’Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R. Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature. 1999 Oct 14;401(6754):670–677.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

October 14, 1999

Volume

401

Issue

6754

Start / End Page

670 / 677

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Transplantation, Heterologous
  • Transcription Factors
  • Repressor Proteins
  • Neurons
  • Nerve Tissue Proteins
  • Neovascularization, Physiologic
  • Neoplasms, Experimental
  • Neoplasm Transplantation
  • Mutation