Abstract
The ganglionic eminence contributes cells to several forebrain structures including the cerebral cortex, for which it provides GABAergic interneurons. Migration of neuronal precursors from the retinoic-acid rich embryonic ganglionic eminence to the cerebral cortex is known to be regulated by several factors, but retinoic acid has not been previously implicated. We found retinoic acid to potently inhibit cell migration in slice preparations of embryonic mouse forebrains, which was reversed by an antagonist of the dopamine-D(2) receptor, whose gene is transcriptionally regulated by retinoic acid. Histone-deacetylase inhibitors, which amplify nuclear receptor-mediated transcription, potentiated the inhibitory effect of retinoic acid. Surprisingly, when retinoic acid signalling was completely blocked with a pan-retinoic acid receptor antagonist, this also decreased cell migration into the cortex, implying that a minimal level of endogenous retinoic acid is necessary for tangential migration. Given these opposing effects of retinoic acid in vitro, the in vivo contribution of retinoic acid to migration was tested by counting GABAergic interneurons in cortices of adult mice with experimental reductions in retinoic acid signalling: a range of perturbations resulted in significant reductions in the numerical density of some GABAergic interneuron subpopulations. These observations suggest functions of retinoic acid in interneuron diversity and organization of cortical excitatory-inhibitory balance.
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Dehydrogenase 1 Family
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Amino Acids / metabolism
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Animals
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Animals, Newborn
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Calbindin 2
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Calbindins
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Cell Movement / drug effects*
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Cell Movement / genetics
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Cerebral Cortex / cytology*
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Cerebral Cortex / embryology
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Cerebral Cortex / growth & development
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Cerebral Cortex / metabolism
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Dopamine Antagonists / pharmacology
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Dose-Response Relationship, Drug
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Enzyme-Linked Immunosorbent Assay / methods
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Female
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Food, Formulated
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / genetics
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Hydroxamic Acids / pharmacology
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Isoenzymes / deficiency
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neurons / drug effects
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Neurons / physiology*
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Organ Culture Techniques
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Parvalbumins / metabolism
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Pregnancy
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Retinal Dehydrogenase / deficiency
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Retinal Dehydrogenase / metabolism
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Retinol-Binding Proteins / deficiency
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S100 Calcium Binding Protein G / metabolism
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Salicylamides / pharmacology
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Telencephalon / cytology*
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Telencephalon / embryology
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Telencephalon / growth & development
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Tretinoin / metabolism
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Tretinoin / pharmacology*
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Valproic Acid / pharmacology
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Vitamin A / metabolism
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gamma-Aminobutyric Acid / metabolism
Substances
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Amino Acids
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Calbindin 2
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Calbindins
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Dopamine Antagonists
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Enzyme Inhibitors
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Hydroxamic Acids
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Isoenzymes
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Parvalbumins
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Retinol-Binding Proteins
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S100 Calcium Binding Protein G
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Salicylamides
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dolaisoleucine
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Vitamin A
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trichostatin A
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gamma-Aminobutyric Acid
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Tretinoin
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Valproic Acid
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Aldehyde Dehydrogenase 1 Family
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ALDH1A1 protein, mouse
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Retinal Dehydrogenase
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retinaldehyde dehydrogenase 3, mouse
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eticlopride