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Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis.

Publication ,  Journal Article
Cash, DE; Bock, CB; Schughart, K; Linney, E; Underhill, TM
Published in: J Cell Biol
January 27, 1997

Retinoic acid is a signaling molecule involved in the regulation of growth and morphogenesis during development. There are three types of nuclear receptors for all-trans retinoic acid in mammals, RAR alpha, RAR beta, and RAR gamma, which transduce the retinoic acid signal by inducing or repressing the transcription of target genes (Leid, M., P. Kastner, and P. Chambon. 1992. Trends Biochem. Sci. 17:427-433). While RAR alpha, RAR beta, and RAR gamma are expressed in distinct but overlapping patterns in the developing mouse limb, their exact role in limb development remains unclear. To better understand the role of retinoic acid receptors in mammalian limb development, we have ectopically expressed a modified RAR alpha with constitutive activity (Balkan, W., G.K. Klintworth, C.B. Bock, and E. Linney. 1992. Dev. Biol. 151:622-625) in the limbs of transgenic mice. Overexpression of the transgene was associated with marked pre- and postaxial limb defects, particularly in the hind limb, where expression of the transgene was consistently seen across the whole anteroposterior axis. The defects displayed in these mice recapitulate, to a large degree, many of the congenital limb malformations observed in the fetuses of dams administered high doses of retinoic acid (Kochhar, D.M. 1973. Teratology. 7:289-295). Further analysis of these transgenic animals showed that the defect in skeletogenesis resided at the level of chondrogenesis. Comparison of the expression of the transgene relative to that of endogenous RAR alpha revealed that downregulation of RAR alpha is important in allowing the chondrogenic phenotype to be expressed. These results demonstrate a specific function for RARalpha in limb development and the regulation of chondroblast differentiation.

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Published In

J Cell Biol

DOI

ISSN

0021-9525

Publication Date

January 27, 1997

Volume

136

Issue

2

Start / End Page

445 / 457

Location

United States

Related Subject Headings

  • Retinoic Acid Receptor alpha
  • Receptors, Retinoic Acid
  • Osteogenesis
  • Mice, Transgenic
  • Mice
  • Mesoderm
  • Male
  • Limb Deformities, Congenital
  • Limb Buds
  • Gene Expression
 

Citation

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Cash, D. E., Bock, C. B., Schughart, K., Linney, E., & Underhill, T. M. (1997). Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis. J Cell Biol, 136(2), 445–457. https://doi.org/10.1083/jcb.136.2.445
Cash, D. E., C. B. Bock, K. Schughart, E. Linney, and T. M. Underhill. “Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis.J Cell Biol 136, no. 2 (January 27, 1997): 445–57. https://doi.org/10.1083/jcb.136.2.445.
Cash DE, Bock CB, Schughart K, Linney E, Underhill TM. Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis. J Cell Biol. 1997 Jan 27;136(2):445–57.
Cash, D. E., et al. “Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis.J Cell Biol, vol. 136, no. 2, Jan. 1997, pp. 445–57. Pubmed, doi:10.1083/jcb.136.2.445.
Cash DE, Bock CB, Schughart K, Linney E, Underhill TM. Retinoic acid receptor alpha function in vertebrate limb skeletogenesis: a modulator of chondrogenesis. J Cell Biol. 1997 Jan 27;136(2):445–457.

Published In

J Cell Biol

DOI

ISSN

0021-9525

Publication Date

January 27, 1997

Volume

136

Issue

2

Start / End Page

445 / 457

Location

United States

Related Subject Headings

  • Retinoic Acid Receptor alpha
  • Receptors, Retinoic Acid
  • Osteogenesis
  • Mice, Transgenic
  • Mice
  • Mesoderm
  • Male
  • Limb Deformities, Congenital
  • Limb Buds
  • Gene Expression