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The Journal of Neuroscience, August 20, 2003, 23(20):7610-7620

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The Meninges Is a Source of Retinoic Acid for the Late-Developing Hindbrain

Jinghua Zhang,¹ Deborah Smith,¹ Miyuki Yamamoto,³ Lanhua Ma,¹ and Peter McCaffery^1,2

¹E. Kennedy Shriver Center and ²Department of Cell Biology, University of Massachusetts Medical School, University of Massachusetts, Waltham, Massachusetts 02452, and ³Institute for Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305, Japan

One general function for retinoic acid (RA) is pattern organization in the CNS. This regulatory factor has an essential role in spinal cord motor neuron and early posterior hindbrain development. In the anterior CNS, however, there is only a limited number of foci of RA synthesis, and less attention has been placed on regions such as the anterior hindbrain where RA synthesizing enzymes are absent. This study shows that a rich source of RA lies around the hindbrain from the RA synthetic enzyme retinaldehyde dehydrogenase-2 (RALDH2) present in the surrounding meninges and mesenchyme by embryonic day 13. RALDH2 is not distributed uniformly throughout the meninges but is restricted to territories over the developing hindbrain, suggesting that RA signaling may be localized to those regions. Further regulation of RA signaling is provided by the presence of a RA sink in the form of the CYP26B1 RA catabolic enzyme expressed in deeper regions of the brain. As a guide to the neural anatomy of hindbrain RA signaling, we used a mouse transgenic for a lacZ reporter gene driven by a RA response element (RAREhsplacZ) to identify regions of RA signaling. This reporter mouse provides evidence that RA signaling in the hindbrain after embryonic day 13 occurs in the regions of the cerebellum and precerebellar system adjacent to sources of RA, including the inferior olive and the pontine nuclei.

View larger version (41K): [in this window] [in a new window]   Figure 1. Pathways of migration of neurons born from the neuroepithelium of the rhombic lip.

 

Key words: pontine nuclei; inferior olive; germinal trigone; cerebellum; precerebellar system; mouse

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Received Feb. 26, 2003; revised Jun. 3, 2003; accepted Jun. 30, 2003.

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