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
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