The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes

Simon J.B. Butt, Vitor H. Sousa, Marc V. Fuccillo, Jens Hjerling-Leffler, Goichi Miyoshi, Shioko Kimura, Gordon Fishell

    Research output: Contribution to journalArticle

    Abstract

    Previous work has demonstrated that the character of mouse cortical interneuron subtypes can be directly related to their embryonic temporal and spatial origins. The relationship between embryonic origin and the character of mature interneurons is likely reflected by the developmental expression of genes that direct cell fate. However, a thorough understanding of the early genetic events that specify subtype identity has been hampered by the perinatal lethality resulting from the loss of genes implicated in the determination of cortical interneurons. Here, we employ a conditional loss-of-function approach to demonstrate that the transcription factor Nkx2-1 is required for the proper specification of specific interneuron subtypes. Removal of this gene at distinct neurogenic time points results in a switch in the subtypes of neurons observed at more mature ages. Our strategy reveals a causal link between the embryonic genetic specification by Nkx2-1 in progenitors and the functional attributes of their neuronal progeny in the mature nervous system.

    Original languageEnglish (US)
    Pages (from-to)722-732
    Number of pages11
    JournalNeuron
    Volume59
    Issue number5
    DOIs
    StatePublished - Sep 11 2008

    Fingerprint

    Interneurons
    Developmental Genes
    Nervous System
    Genes
    Transcription Factors
    Neurons

    Keywords

    • DEVBIO
    • SIGNALING

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    Butt, S. J. B., Sousa, V. H., Fuccillo, M. V., Hjerling-Leffler, J., Miyoshi, G., Kimura, S., & Fishell, G. (2008). The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes. Neuron, 59(5), 722-732. https://doi.org/10.1016/j.neuron.2008.07.031

    The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes. / Butt, Simon J.B.; Sousa, Vitor H.; Fuccillo, Marc V.; Hjerling-Leffler, Jens; Miyoshi, Goichi; Kimura, Shioko; Fishell, Gordon.

    In: Neuron, Vol. 59, No. 5, 11.09.2008, p. 722-732.

    Research output: Contribution to journalArticle

    Butt, SJB, Sousa, VH, Fuccillo, MV, Hjerling-Leffler, J, Miyoshi, G, Kimura, S & Fishell, G 2008, 'The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes', Neuron, vol. 59, no. 5, pp. 722-732. https://doi.org/10.1016/j.neuron.2008.07.031
    Butt SJB, Sousa VH, Fuccillo MV, Hjerling-Leffler J, Miyoshi G, Kimura S et al. The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes. Neuron. 2008 Sep 11;59(5):722-732. https://doi.org/10.1016/j.neuron.2008.07.031
    Butt, Simon J.B. ; Sousa, Vitor H. ; Fuccillo, Marc V. ; Hjerling-Leffler, Jens ; Miyoshi, Goichi ; Kimura, Shioko ; Fishell, Gordon. / The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes. In: Neuron. 2008 ; Vol. 59, No. 5. pp. 722-732.
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