Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors

被引：188

作者：

Nobrega-Pereira, Sandrina ^{[1
,2
,3
]}

Kessaris, Nicoletta ^{[4
,5
]}

Du, Tonggong ^{[6
]}

Kimura, Shioko ^{[7
]}

Anderson, Stewart A. ^{[6
]}

Marin, Oscar ^{[1
,2
]}

机构：

[1] CSIC, Inst Neurociencias Alicante, Sant Joan dAlacant 03550, Spain

[2] Univ Miguel Hernandez, Sant Joan dAlacant 03550, Spain

[3] Univ Coimbra, Programme Expt Biol & Biomed, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal

[4] UCL, Wolfson Inst Biomed Res, London WC1E 6AE, England

[5] UCL, Dept Cell & Dev Biol, London WC1E 6AE, England

[6] Cornell Univ, Dept Psychiat, Weill Med Coll, New York, NY 10021 USA

[7] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA

来源：

NEURON | 2008年 / 59卷 / 05期

基金：

英国医学研究理事会; 欧洲研究理事会;

关键词：

D O I：

10.1016/j.neuron.2008.07.024

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 post-mitotic function of Nkx2-1 in the migration of interneurons originating in the MGE. Experimental manipulations and mouse genetics show that down-regulation 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.

引用

页码：733 / 745

页数：13

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