Once and again: Retinoic acid signaling in the developing and regenerating olfactory pathway

Retinoic acid (RA), a member of the steroid/thyroid superfamily of signaling molecules, is an essential regulator of morphogenesis, differentiation, and regeneration in the mammalian olfactory pathway. RA‐mediated teratogenesis dramatically alters olfactory pathway development, presumably by disrupt...

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Bibliographic Details
Published in:Journal of neurobiology 2006-06, Vol.66 (7), p.653-676
Main Authors: Rawson, N.E., LaMantia, A.‐S.
Format: Article
Language:English
Subjects:
Animals
embryonic induction
Humans
olfactory bulb
Olfactory Bulb - embryology
Olfactory Bulb - physiology
olfactory epithelium
Olfactory Mucosa - physiology
Olfactory Pathways - embryology
Olfactory Pathways - physiology
Signal Transduction - physiology
stem cells
Tretinoin - physiology
vitamin A
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Summary:Retinoic acid (RA), a member of the steroid/thyroid superfamily of signaling molecules, is an essential regulator of morphogenesis, differentiation, and regeneration in the mammalian olfactory pathway. RA‐mediated teratogenesis dramatically alters olfactory pathway development, presumably by disrupting retinoid‐mediated inductive signaling that influences initial olfactory epithelium (OE) and bulb (OB) morphogenesis. Subsequently, RA modulates the genesis, growth, or stability of subsets of OE cells and OB interneurons. RA receptors, cofactors, and synthetic enzymes are expressed in the OE, OB, and anterior subventricular zone (SVZ), the site of neural precursors that generate new OB interneurons throughout adulthood. Their expression apparently accommodates RA signaling in OE cells, OB interneurons, and slowly dividing SVZ neural precursors. Deficiency of vitamin A, the dietary metabolic RA precursor, leads to cytological changes in the OE, as well as olfactory sensory deficits. Vitamin A therapy in animals with olfactory system damage can accelerate functional recovery. RA‐related pathology as well as its potential therapeutic activity may reflect endogenous retinoid regulation of neuronal differentiation, stability, or regeneration in the olfactory pathway from embryogenesis through adulthood. These influences may be in register with retinoid effects on immune responses, metabolism, and modulation of food intake. © 2006 Wiley Periodicals, Inc. J Neurobiol 66: 653–676, 2006
ISSN:0022-3034
1097-4695
DOI:10.1002/neu.20236