Retinaldehyde dehydrogenase 2 and HoxC8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons, and the correct distribution of Islet1+ motoneurons

Julien Vermot, Brigitte Schuhbaur, Hervé Le Mouellic, Peter John Andrew McCaffery, Jean-Marie Garnier, Didier Hentsch, Philippe Brûlet, Karen Niederreither, Pierre Chambon, Pascal Dollé, Isabelle Le Roux

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Retinoic acid (RA) activity plays sequential roles during the development of the ventral spinal cord. Here, we have investigated the functions of local RA synthesis in the process of motoneuron specification and early differentiation using a conditional knockout strategy that ablates the function of the retinaldehyde dehydrogenase 2 (Raldh2) synthesizing enzyme essentially in brachial motoneurons, and later in mesenchymal cells at the base of the forelimb. Mutant (Raldh2(L-/-)) embryos display an early embryonic loss of a subset of Lim1+ brachial motoneurons, a mispositioning of Islet1+ neurons and inappropriate axonal projections of one of the nerves innervating extensor limb muscles, which lead to an adult forepaw neuromuscular defect. The molecular basis of the Raldh2(L-/-) phenotype relies in part on the deregulation of Hoxc8, which in turn regulates the RA receptor RAR beta. We further show that Hoxc8 mutant mice, which exhibit a similar congenital forepaw defect, display at embryonic stages molecular defects that phenocopy the Raldh2(L-/-) motoneuron abnormalities. Thus, interdependent RA signaling and Hox gene functions are required for the specification of brachial motoneurons in the mouse.

Original languageEnglish
Pages (from-to)1611-1621
Number of pages11
JournalDevelopment
Volume132
Issue number7
DOIs
Publication statusPublished - Apr 2005

Keywords

  • aldehyde oxidoreductases
  • animals
  • homeodomain proteins
  • mice
  • mice, knockout
  • motor neurons
  • mutation
  • spinal cord
  • transcription factors
  • retinoic acid
  • Raldh2
  • hox genes
  • lim1
  • islet1
  • mouse

Cite this

Vermot, J., Schuhbaur, B., Le Mouellic, H., McCaffery, P. J. A., Garnier, J-M., Hentsch, D., Brûlet, P., Niederreither, K., Chambon, P., Dollé, P., & Le Roux, I. (2005). Retinaldehyde dehydrogenase 2 and HoxC8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons, and the correct distribution of Islet1+ motoneurons. Development, 132(7), 1611-1621. https://doi.org/10.1242/dev.01718