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Transcriptional repression by FEZF2 restricts alternative identities of cortical projection neurons
- Source :
- Cell reports, Cell reports, vol 35, iss 12
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- SUMMARY Projection neuron subtype identities in the cerebral cortex are established by expressing pan-cortical and subtype-specific effector genes that execute terminal differentiation programs bestowing neurons with a glutamatergic neuron phenotype and subtype-specific morphology, physiology, and axonal projections. Whether pan-cortical glutamatergic and subtype-specific characteristics are regulated by the same genes or controlled by distinct programs remains largely unknown. Here, we show that FEZF2 functions as a transcriptional repressor, and it regulates subtype-specific identities of both corticothalamic and subcerebral neurons by selectively repressing expression of genes inappropriate for each neuronal subtype. We report that TLE4, specifically expressed in layer 6 corticothalamic neurons, is recruited by FEZF2 to inhibit layer 5 subcerebral neuronal genes. Together with previous studies, our results indicate that a cortical glutamatergic identity is specified by multiple parallel pathways active in progenitor cells, whereas projection neuron subtype-specific identity is achieved through selectively repressing genes associated with alternate identities in differentiating neurons.<br />Graphical Abstract<br />In brief Layer 6 corticothalamic and layer 5 subcerebral projection neurons connect the cerebral cortex to the thalamus and brainstem and spinal cord, respectively. Tsyporin et al. report that the transcription factor FEZF2 specifies the development of these neuronal identities by repressing expression of genes associated with alternate projection neuron subtypes.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
Medical Physiology
transcriptional repressor
Mice
0302 clinical medicine
transcription factor
Cerebral Cortex
Mice, Knockout
Neurons
cell fate
Effector
Fezf2
Cell Differentiation
Phenotype
DNA-Binding Proteins
subtype identity
medicine.anatomical_structure
Cerebral cortex
Neurological
Stem Cell Research - Nonembryonic - Non-Human
Transcription
Biotechnology
Protein Binding
Knockout
1.1 Normal biological development and functioning
Mitosis
Nerve Tissue Proteins
Cell fate determination
Biology
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Glutamatergic
Genetic
Underpinning research
Genetics
medicine
Animals
Transcription factor
Gene
Alleles
Neurosciences
Tle4
Stem Cell Research
cortical projection neurons
Electrophysiological Phenomena
Repressor Proteins
030104 developmental biology
Gene Expression Regulation
nervous system
Biochemistry and Cell Biology
Neuron
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....65c98564942f72266044194142f2c644