Abstract
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.
Original language | English (US) |
---|---|
Article number | 109269 |
Journal | Cell Reports |
Volume | 35 |
Issue number | 12 |
DOIs | |
State | Published - Jun 22 2021 |
Keywords
- Fezf2
- Tle4
- cell fate
- cerebral cortex
- cortical projection neurons
- subtype identity
- transcription factor
- transcriptional repressor
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology