The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes.
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.
Butt
Simon J B
SJ
Smilow Neuroscience Program and the Department of Cell Biology, New York University, New York, NY 10016, USA.
Sousa
Vitor H
VH
Fuccillo
Marc V
MV
Hjerling-Leffler
Jens
J
Miyoshi
Goichi
G
Kimura
Shioko
S
Fishell
Gord
G
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology*; D004569:Electroencephalography; D004622:Embryo, Mammalian; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000145:classification* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D012640:Seizures / Q000235:genetics / Q000503:physiopathology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004965:Estrogen Antagonists; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D013629:Tamoxifen; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D001616:beta-Galactosidase; C000614414:Nkx2-1 protein, mouse; C485184:enhanced green fluorescent protein
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