Abstract
The homeodomain transcription factor Nkx2-1 plays key roles in the developing telencephalon, where it regulates the identity of progenitor cells in the medial ganglionic eminence (MGE) and mediates the specification of several classes of GABAergic and cholinergic neurons. Here, we have investigated the postmitotic function of Nkx2-1 in the migration of interneurons originating in the MGE. Experimental manipulations and mouse genetics show that downregulation of Nkx2-1 expression in postmitotic cells is necessary for the migration of interneurons to the cortex, whereas maintenance of Nkx2-1 expression is required for interneuron migration to the striatum. Nkx2-1 exerts this role in the migration of MGE-derived interneurons by directly regulating the expression of a guidance receptor, Neuropilin-2, which enables interneurons to invade the developing striatum. Our results demonstrate a role for the cell-fate determinant Nkx2-1 in regulating neuronal migration by direct transcriptional regulation of guidance receptors in postmitotic cells.
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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Animals
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Cell Count / methods
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Cell Differentiation / physiology*
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Cell Movement / physiology*
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Chromatin Immunoprecipitation / methods
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Electroporation / methods
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Embryo, Mammalian
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Gene Expression Regulation, Developmental / physiology*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Interneurons / physiology*
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LIM-Homeodomain Proteins
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Luminescent Proteins / genetics
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Luminescent Proteins / metabolism
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Median Eminence / cytology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neuropilin-2 / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Organ Culture Techniques
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Thyroid Nuclear Factor 1
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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Homeodomain Proteins
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LHX6 protein, mouse
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LIM-Homeodomain Proteins
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Luminescent Proteins
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Nerve Tissue Proteins
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Neuropilin-2
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Nkx2-1 protein, mouse
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Nuclear Proteins
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Thyroid Nuclear Factor 1
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Transcription Factors