The Requirement of Nkx2-1 in the Temporal Specification of Cortical Interneuron Subtypes
Autor: | Gordon Fishell, Vitor H. Sousa, Marc V. Fuccillo, Simon J. B. Butt, Shioko Kimura, Jens Hjerling-Leffler, Goichi Miyoshi |
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Rok vydání: | 2008 |
Předmět: |
Nervous system
Male Cellular differentiation Thyroid Nuclear Factor 1 DEVBIO medicine.disease_cause Mice 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors Cerebral Cortex 0303 health sciences Mutation General Neuroscience Stem Cells Age Factors Estrogen Antagonists Gene Expression Regulation Developmental Nuclear Proteins Cell Differentiation Electroencephalography respiratory system medicine.anatomical_structure SIGNALING Cerebral cortex embryonic structures cardiovascular system Female Interneuron Neuroscience(all) Green Fluorescent Proteins Mice Transgenic Nerve Tissue Proteins Biology Cell fate determination Article 03 medical and health sciences stomatognathic system Interneurons Seizures medicine Animals Transcription factor 030304 developmental biology Body Patterning Embryo Mammalian beta-Galactosidase Embryonic stem cell Tamoxifen Animals Newborn nervous system Neuroscience 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Neuron. 59(5):722-732 |
ISSN: | 0896-6273 |
DOI: | 10.1016/j.neuron.2008.07.031 |
Popis: | SummaryPrevious 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. |
Databáze: | OpenAIRE |
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