Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis

Astroglial cells are essential components of the neurogenic niches within the central nervous system. Emerging evidence suggests that they are among the key regulators of postnatal neurogenesis. Although astrocytes have been demonstrated to possess the potential to instruct stem cells to adopt a neu...

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Bibliographic Details
Published in:The FASEB journal 2007-08, Vol.21 (10), p.2496-2509
Main Authors: Környei, Z, Gócza, E, Rühl, R, Orsolits, B, Vörös, E, Szabó, B, Vágovits, B, Madarász, E
Format: Article
Language:English
Subjects:
Aging
Animals
Animals, Newborn
astrocyte
Astrocytes - physiology
Brain - growth & development
Cell Differentiation
Central Nervous System - physiology
Genes, Reporter
Mice
Mice, Transgenic
Morphogenesis
Neuroglia - physiology
neuronal differentiation
Neurons - cytology
Neurons - physiology
stem cell
Stem Cells - physiology
Tretinoin - physiology
Tumor Suppressor Protein p53 - deficiency
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Summary:Astroglial cells are essential components of the neurogenic niches within the central nervous system. Emerging evidence suggests that they are among the key regulators of postnatal neurogenesis. Although astrocytes have been demonstrated to possess the potential to instruct stem cells to adopt a neuronal fate, little is known about the nature of the glia-derived instructive signals. Here we propose that all-trans retinoic acid, one of the most powerful morphogenic molecules regulating neuronal cell fate commitment, may be one of the glia-derived factors directing astroglia-induced neurogenesis. According to data obtained from several complementary approaches, we show that cultured astrocytes express the key enzyme mRNAs of retinoic acid biosynthesis and actively produce all-trans retinoic acid. We show that blockage of retinoic acid signaling by the pan-RAR antagonist AGN193109 prevents glia-induced neuron formation by noncommitted stem cells. Therefore, we provide strong in vitro evidence for retinoic acid action in astroglia-induced neuronal differentiation.--Környei, Z., Gócza, E., Rühl, R., Vörös, E., Orsolits, B., Szabó, B., Vágovits, B., Madarász, E. Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.06-7756com