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Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites.

Publication ,  Journal Article
Wang, Y; Jones, FS; Krushel, LA; Edelman, GM
Published in: Proc Natl Acad Sci U S A
March 5, 1996

During development of the vertebrate nervous system, the neural cell adhesion molecule (N-CAM) is expressed in a defined spatiotemporal pattern. We have proposed that the expression of N-CAM is controlled, in part, by proteins encoded by homeobox genes. This hypothesis has been supported by previous in vitro experiments showing that products of homeobox genes can both bind to and transactivate the N-CAM promoter via two homeodomain binding sites, HBS-I and HBS-II. We have now tested the hypothesis that the N-CAM gene is a target of homeodomain proteins in vivo by using transgenic mice containing native and mutated N-CAM promoter constructs linked to a beta-galactosidase reporter gene. Segments of the 5' flanking region of the mouse N-CAM gene were sufficient to direct expression of the reporter gene in the central nervous system in a pattern consistent with that of the endogenous N-CAM gene. For example, at embryonic day (E) 11, beta-galactosidase staining was found in postmitotic neurons in dorsolateral and ventrolateral regions of the spinal cord; at E14.5, staining was seen in these neurons throughout the spinal cord. In contrast, mice carrying an N-CAM promoter-reporter construct with mutations in both homeodomain binding sites (HBS-I and HBS-II) showed altered expression patterns in the spinal cord. At E11, beta-galactosidase expression was seen in the ventrolateral spinal cord, but was absent in the dorsolateral areas, and at E 14.5, beta-galactosidase expression was no longer detected in any cells of the cord. Homeodomain binding sites found in the N-CAM promoter thus appear to be important in determining specific expression patterns of N-CAM along the dorsoventral axis in the developing spinal cord. These experiments suggest that the N-CAM gene is an in vivo target of homeobox gene products in vertebrates.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 5, 1996

Volume

93

Issue

5

Start / End Page

1892 / 1896

Location

United States

Related Subject Headings

  • Spinal Cord
  • Promoter Regions, Genetic
  • Neural Cell Adhesion Molecules
  • Nervous System
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice
  • Gene Expression Regulation, Developmental
  • Base Sequence
  • Animals
 

Citation

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Wang, Y., Jones, F. S., Krushel, L. A., & Edelman, G. M. (1996). Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites. Proc Natl Acad Sci U S A, 93(5), 1892–1896. https://doi.org/10.1073/pnas.93.5.1892
Wang, Y., F. S. Jones, L. A. Krushel, and G. M. Edelman. “Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites.Proc Natl Acad Sci U S A 93, no. 5 (March 5, 1996): 1892–96. https://doi.org/10.1073/pnas.93.5.1892.
Wang Y, Jones FS, Krushel LA, Edelman GM. Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1892–6.
Wang, Y., et al. “Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites.Proc Natl Acad Sci U S A, vol. 93, no. 5, Mar. 1996, pp. 1892–96. Pubmed, doi:10.1073/pnas.93.5.1892.
Wang Y, Jones FS, Krushel LA, Edelman GM. Embryonic expression patterns of the neural cell adhesion molecule gene are regulated by homeodomain binding sites. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1892–1896.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 5, 1996

Volume

93

Issue

5

Start / End Page

1892 / 1896

Location

United States

Related Subject Headings

  • Spinal Cord
  • Promoter Regions, Genetic
  • Neural Cell Adhesion Molecules
  • Nervous System
  • Molecular Sequence Data
  • Mice, Transgenic
  • Mice
  • Gene Expression Regulation, Developmental
  • Base Sequence
  • Animals