MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice

Minhan Ka; Jeffrey J. Moffat; Woo Yang Kim

doi:10.1093/cercor/bhw319

MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice

Minhan Ka, Jeffrey J. Moffat, Woo Yang Kim

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain.

Original language	English (US)
Pages (from-to)	5525-5538
Number of pages	14
Journal	Cerebral Cortex
Volume	27
Issue number	12
DOIs	https://doi.org/10.1093/cercor/bhw319
State	Published - Dec 1 2017

Keywords

MACF1
interneuron
leading process
microtubule
migration

ASJC Scopus subject areas

Cognitive Neuroscience
Cellular and Molecular Neuroscience

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10.1093/cercor/bhw319

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title = "MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice",

abstract = "GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain.",

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author = "Minhan Ka and Moffat, {Jeffrey J.} and Kim, {Woo Yang}",

note = "Funding Information: Research reported in this publication was supported by an award from the National Institute of Neurological Disorders and Stroke of the National Institute of Health under award number R01NS091220 and an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103471 to W.Y.K. Publisher Copyright: {\textcopyright} 2016 The Author.",

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AU - Ka, Minhan

AU - Moffat, Jeffrey J.

AU - Kim, Woo Yang

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N2 - GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain.

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MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice

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