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
Open Access
- 1 April 2005
- journal article
- Published by The Company of Biologists in Development
- Vol. 132 (7), 1611-1621
- https://doi.org/10.1242/dev.01718
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 (Raldh2L–/–) 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 Raldh2L–/– phenotype relies in part on the deregulation of Hoxc8, which in turn regulates the RA receptor RARβ. We further show that Hoxc8 mutant mice, which exhibit a similar congenital forepaw defect, display at embryonic stages molecular defects that phenocopy the Raldh2L–/– motoneuron abnormalities. Thus, interdependent RA signaling and Hox gene functions are required for the specification of brachial motoneurons in the mouse.Keywords
This publication has 47 references indexed in Scilit:
- Retinoids Run RampantNeuron, 2003
- Role of EphA4 in defining the position of a motoneuron pool within the spinal cordJournal of Comparative Neurology, 2003
- The retinoic acid-metabolizing enzyme, CYP26A1, is essential for normal hindbrain patterning, vertebral identity, and development of posterior structuresGenes & Development, 2001
- Restricted expression and retinoic acid-induced downregulation of the retinaldehyde dehydrogenase type 2 (RALDH-2) gene during mouse developmentMechanisms of Development, 1997
- Retinoid signaling and the generation of regional and cellular diversity in the embryonic mouse spinal cordDevelopmental Dynamics, 1995
- Characterisation of the Sek‐1 receptor tyrosine kinaseFEBS Letters, 1995
- Specifying the target identity of motoneuronsBioEssays, 1995
- Expression of a retinoic acid response element-hsplacZ transgene defines specific domains of transcriptional activity during mouse embryogenesis.Genes & Development, 1991
- Determination of Primary Motoneuron Identity in Developing Zebrafish EmbryosScience, 1991
- Identification of a retinoic acid responsive element in the retinoic acid receptor & beta;geneNature, 1990