Retinoic Acid Signaling Identifies a Distinct Precursor Population in the Developing and Adult Forebrain

We asked whether retinoic acid (RA), an established transcriptional regulator in regenerating and developing tissues, acts directly on distinct cell classes in the mature or embryonic forebrain. We identified a subset of slowly dividing precursors in the adult subventricular zone (SVZ) that is trans...

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Bibliographic Details
Published in:The Journal of neuroscience 2005-08, Vol.25 (33), p.7636-7647
Main Authors: Haskell, Gloria Thompson, LaMantia, Anthony-Samuel
Format: Article
Language:English
Subjects:
Aging - metabolism
Aging - physiology
Animals
Cell Differentiation - physiology
Cells, Cultured
Cellular/Molecular
Female
Male
Mice
Mice, Inbred ICR
Mice, Transgenic
Pregnancy
Prosencephalon - cytology
Prosencephalon - embryology
Prosencephalon - growth & development
Prosencephalon - metabolism
Signal Transduction - physiology
Stem Cells - cytology
Stem Cells - metabolism
Tretinoin - physiology
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Summary:We asked whether retinoic acid (RA), an established transcriptional regulator in regenerating and developing tissues, acts directly on distinct cell classes in the mature or embryonic forebrain. We identified a subset of slowly dividing precursors in the adult subventricular zone (SVZ) that is transcriptionally activated by RA. Most of these cells express glial fibrillary acidic protein, a smaller subset expresses the epidermal growth factor receptor, a few are terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling positive, and they can be mitotically labeled by sustained rather than acute bromodeoxyuridine exposure. RA activation in similar cells in SVZ-derived neurospheres depends on retinoid synthesis from the premetabolite retinol. The apparent influence of RA on precursors in vitro is consistent with key properties of RA activation in the SVZ; in neurospheres, altered retinoid signaling elicits neither cell death nor an acute increase in cell proliferation. There is apparent continuity of RA signaling in the forebrain throughout life. RA-activated, proliferative precursors with radial glial characteristics are found in the dorsal lateral ganglionic eminence and ventrolateral palliumembryonic rudiments of the SVZ. Thus, endogenous RA signaling distinguishes subsets of neural precursors with glial characteristics in a consistent region of the adult and developing forebrain.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0485-05.2005