Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons

Miyoshi, G., Young, A., Petros, T., Karayannis, T., McKenzie Chang, M., Lavado, A., Iwano, T., Nakajima, M., Taniguchi, H., Huang, Z. J., Heintz, N., Oliver, G., Matsuzaki, F., Machold, R. P., Fishell, G. (2015) Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons. J Neurosci, 35 (37). pp. 12869-89. ISSN 1529-2401 (Electronic)0270-6474 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/26377473
DOI: 10.1523/jneurosci.1164-15.2015

Abstract

Neurogliaform (RELN+) and bipolar (VIP+) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties. SIGNIFICANCE STATEMENT: Despite the recognition that 30% of GABAergic cortical interneurons originate from the caudal ganglionic eminence (CGE), to date, a specific transcriptional program that selectively regulates the development of these populations has not yet been identified. Moreover, while CGE-derived interneurons display unique patterns of tangential and radial migration and preferentially populate the superficial layers of the cortex, identification of a molecular program that controls these events is lacking.Here, we demonstrate that the homeodomain transcription factor Prox1 is expressed in postmitotic CGE-derived cortical interneuron precursors and is maintained into adulthood. We found that Prox1 function is differentially required during both embryonic and postnatal stages of development to direct the migration, differentiation, circuit integration, and maintenance programs within distinct subtypes of CGE-derived interneurons.

Item Type: Paper
Uncontrolled Keywords: Reln Vip bipolar mouse genetics neurogliaform transcription
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: Matt Covey
Date Deposited: 18 Sep 2015 16:41
Last Modified: 09 Jan 2017 20:17
PMCID: PMC4571608
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31872

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