1. Transcriptional repression by FEZF2 restricts alternative identities of cortical projection neurons
- Author
-
Susan K. McConnell, Zhengang Yang, Antoine Nehme, Daisy Gallardo, Thomas S. Finn, Guoping Liu, Bin Chen, Shenfeng Qiu, Solomon Katzman, Nenad Sestan, Xiaokuang Ma, Jacqueline M. Roberts, Liora Huebner, Jeremiah Tsyporin, David Tastad, and Amr Makhamreh
- 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 - 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., Graphical Abstract, 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.
- Published
- 2021