The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes.

Butt SJB., Sousa VH., Fuccillo MV., Hjerling-Leffler J., Miyoshi G., Kimura S., Fishell G.

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.

DOI

10.1016/j.neuron.2008.07.031

Type

Journal article

Journal

Neuron

Publication Date

11/09/2008

Volume

59

Pages

722 - 732

Keywords

Age Factors, Animals, Animals, Newborn, Basic Helix-Loop-Helix Transcription Factors, Body Patterning, Cell Differentiation, Cerebral Cortex, Electroencephalography, Embryo, Mammalian, Estrogen Antagonists, Female, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Interneurons, Male, Mice, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Seizures, Stem Cells, Tamoxifen, Thyroid Nuclear Factor 1, Transcription Factors, beta-Galactosidase

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