Gene expression in cortical interneuron precursors is prescient of their mature function

Renata Batista-Brito, Robert MacHold, Corinna Klein, Gordon Fishell

Research output: Contribution to journalArticle

Abstract

At present little is known about the developmental mechanisms that give rise to inhibitory γ-aminobutyric acidergic interneurons of the neocortex or the timing of their subtype specification. As such, we performed a gene expression microarray analysis on cortical interneuron precursors isolated through their expression of a Dlx5/6Cre-IRES-EGFP transgene. We purified these precursors from the embryonic mouse neocortex at E13.5 and E15.5 by sorting of enhanced green fluorescent protein-expressing cells. We identified novel transcription factors, neuropeptides, and cell surface genes whose expression is highly enriched in embryonic cortical interneuron precursors. Our identification of many of the genes known to be selectively enriched within cortical interneurons validated the efficacy of our approach. Surprisingly, we find that subpopulations of migrating cortical interneurons express genes encoding for proteins characteristic of mature interneuron subtypes as early as E13.5. These results provide support for the idea that many of the genes characteristic of specific cortical interneuron subtypes are evident prior to their functional integration into cortical microcircuitry. They suggest interneurons are already relegated to specific genetic subtypes shortly after they become postmitotic. Moreover, our work has revealed that many of the genes expressed in cortical interneuron precursors have been independently linked to neurological disorders in both mice and humans.

Original languageEnglish (US)
Pages (from-to)2306-2317
Number of pages12
JournalCerebral Cortex
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Interneurons
Gene Expression
Neocortex
Genes
Microarray Analysis
Nervous System Diseases
Neuropeptides
Transgenes
Transcription Factors

Keywords

  • Cortical interneurons
  • Subtype specification
  • Transcriptional code

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Gene expression in cortical interneuron precursors is prescient of their mature function. / Batista-Brito, Renata; MacHold, Robert; Klein, Corinna; Fishell, Gordon.

In: Cerebral Cortex, Vol. 18, No. 10, 01.10.2008, p. 2306-2317.

Research output: Contribution to journalArticle

Batista-Brito, Renata ; MacHold, Robert ; Klein, Corinna ; Fishell, Gordon. / Gene expression in cortical interneuron precursors is prescient of their mature function. In: Cerebral Cortex. 2008 ; Vol. 18, No. 10. pp. 2306-2317.
@article{0af9c5258f4b4878aa1e8daac3979d4b,
title = "Gene expression in cortical interneuron precursors is prescient of their mature function",
abstract = "At present little is known about the developmental mechanisms that give rise to inhibitory γ-aminobutyric acidergic interneurons of the neocortex or the timing of their subtype specification. As such, we performed a gene expression microarray analysis on cortical interneuron precursors isolated through their expression of a Dlx5/6Cre-IRES-EGFP transgene. We purified these precursors from the embryonic mouse neocortex at E13.5 and E15.5 by sorting of enhanced green fluorescent protein-expressing cells. We identified novel transcription factors, neuropeptides, and cell surface genes whose expression is highly enriched in embryonic cortical interneuron precursors. Our identification of many of the genes known to be selectively enriched within cortical interneurons validated the efficacy of our approach. Surprisingly, we find that subpopulations of migrating cortical interneurons express genes encoding for proteins characteristic of mature interneuron subtypes as early as E13.5. These results provide support for the idea that many of the genes characteristic of specific cortical interneuron subtypes are evident prior to their functional integration into cortical microcircuitry. They suggest interneurons are already relegated to specific genetic subtypes shortly after they become postmitotic. Moreover, our work has revealed that many of the genes expressed in cortical interneuron precursors have been independently linked to neurological disorders in both mice and humans.",
keywords = "Cortical interneurons, Subtype specification, Transcriptional code",
author = "Renata Batista-Brito and Robert MacHold and Corinna Klein and Gordon Fishell",
year = "2008",
month = "10",
day = "1",
doi = "10.1093/cercor/bhm258",
language = "English (US)",
volume = "18",
pages = "2306--2317",
journal = "Cerebral Cortex",
issn = "1047-3211",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Gene expression in cortical interneuron precursors is prescient of their mature function

AU - Batista-Brito, Renata

AU - MacHold, Robert

AU - Klein, Corinna

AU - Fishell, Gordon

PY - 2008/10/1

Y1 - 2008/10/1

N2 - At present little is known about the developmental mechanisms that give rise to inhibitory γ-aminobutyric acidergic interneurons of the neocortex or the timing of their subtype specification. As such, we performed a gene expression microarray analysis on cortical interneuron precursors isolated through their expression of a Dlx5/6Cre-IRES-EGFP transgene. We purified these precursors from the embryonic mouse neocortex at E13.5 and E15.5 by sorting of enhanced green fluorescent protein-expressing cells. We identified novel transcription factors, neuropeptides, and cell surface genes whose expression is highly enriched in embryonic cortical interneuron precursors. Our identification of many of the genes known to be selectively enriched within cortical interneurons validated the efficacy of our approach. Surprisingly, we find that subpopulations of migrating cortical interneurons express genes encoding for proteins characteristic of mature interneuron subtypes as early as E13.5. These results provide support for the idea that many of the genes characteristic of specific cortical interneuron subtypes are evident prior to their functional integration into cortical microcircuitry. They suggest interneurons are already relegated to specific genetic subtypes shortly after they become postmitotic. Moreover, our work has revealed that many of the genes expressed in cortical interneuron precursors have been independently linked to neurological disorders in both mice and humans.

AB - At present little is known about the developmental mechanisms that give rise to inhibitory γ-aminobutyric acidergic interneurons of the neocortex or the timing of their subtype specification. As such, we performed a gene expression microarray analysis on cortical interneuron precursors isolated through their expression of a Dlx5/6Cre-IRES-EGFP transgene. We purified these precursors from the embryonic mouse neocortex at E13.5 and E15.5 by sorting of enhanced green fluorescent protein-expressing cells. We identified novel transcription factors, neuropeptides, and cell surface genes whose expression is highly enriched in embryonic cortical interneuron precursors. Our identification of many of the genes known to be selectively enriched within cortical interneurons validated the efficacy of our approach. Surprisingly, we find that subpopulations of migrating cortical interneurons express genes encoding for proteins characteristic of mature interneuron subtypes as early as E13.5. These results provide support for the idea that many of the genes characteristic of specific cortical interneuron subtypes are evident prior to their functional integration into cortical microcircuitry. They suggest interneurons are already relegated to specific genetic subtypes shortly after they become postmitotic. Moreover, our work has revealed that many of the genes expressed in cortical interneuron precursors have been independently linked to neurological disorders in both mice and humans.

KW - Cortical interneurons

KW - Subtype specification

KW - Transcriptional code

UR - http://www.scopus.com/inward/record.url?scp=58149195774&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149195774&partnerID=8YFLogxK

U2 - 10.1093/cercor/bhm258

DO - 10.1093/cercor/bhm258

M3 - Article

VL - 18

SP - 2306

EP - 2317

JO - Cerebral Cortex

JF - Cerebral Cortex

SN - 1047-3211

IS - 10

ER -