Drs. Chatzi and Cunningham contributed equally to this manuscript.
Investigation of retinoic acid function during embryonic brain development using retinaldehyde-rescued Rdh10 knockout mice
Article first published online: 22 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 242, Issue 9, pages 1056–1065, September 2013
How to Cite
Chatzi, C., Cunningham, T. J. and Duester, G. (2013), Investigation of retinoic acid function during embryonic brain development using retinaldehyde-rescued Rdh10 knockout mice. Dev. Dyn., 242: 1056–1065. doi: 10.1002/dvdy.23999
- Issue published online: 20 AUG 2013
- Article first published online: 22 JUL 2013
- Accepted manuscript online: 13 JUN 2013 03:41AM EST
- Manuscript Accepted: 1 JUN 2013
- Manuscript Revised: 22 MAY 2013
- Manuscript Received: 13 APR 2013
- National Institutes of Health. Grant Number: OD011181
- Rdh10 knockout;
- retinoic acid;
Background: Retinoic acid (RA) signaling controls patterning and neuronal differentiation within the hindbrain, but forebrain RA function remains controversial. RA is produced from metabolism of retinol to retinaldehyde by retinol dehydrogenase (RDH), followed by metabolism of retinaldehyde to RA by retinaldehyde dehydrogenase (RALDH). Previous studies on Raldh2−/− and Raldh3−/− mice demonstrated an RA requirement for γ-aminobutyric acid (GABA)ergic and dopaminergic differentiation in forebrain basal ganglia, but no RA requirement was observed during early forebrain patterning or subsequent forebrain cortical expansion. However, other studies suggested that RA controls forebrain patterning, and analysis of ethylnitrosourea-induced Rdh10 mutants suggested that RA synthesized in the meninges stimulates forebrain cortical expansion. Results: We generated Rdh10−/− mouse embryos that lack RA activity early in the head and later in the meninges. We observed defects in hindbrain patterning and eye RA signaling, but early forebrain patterning was unaffected. Retinaldehyde treatment of Rdh10−/− embryos from E7–E9 rescues a cranial skeletal defect, resulting in E14.5 embryos lacking meningeal RA activity but maintaining normal forebrain shape and cortical expansion. Conclusions: Rdh10−/− embryos demonstrate that RA controls hindbrain but not early forebrain patterning, while studies on retinaldehyde-rescued Rdh10−/− embryos show that meningeal RA synthesis is unnecessary to stimulate forebrain cortical expansion. Developmental Dynamics 242:1056–1065, 2013. © 2013 Wiley Periodicals, Inc.