@article{4b10d698449043738907335f866e48ea,
title = "Transcriptional repression by FEZF2 restricts alternative identities of cortical projection neurons",
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.",
keywords = "Fezf2, Tle4, cell fate, cerebral cortex, cortical projection neurons, subtype identity, transcription factor, transcriptional repressor",
author = "Jeremiah Tsyporin and David Tastad and Xiaokuang Ma and Antoine Nehme and Thomas Finn and Liora Huebner and Guoping Liu and Daisy Gallardo and Amr Makhamreh and Roberts, {Jacqueline M.} and Solomon Katzman and Nenad Sestan and McConnell, {Susan K.} and Zhengang Yang and Shenfeng Qiu and Bin Chen",
note = "Funding Information: This study was supported by grants to B.C. (NIH R01 MH094589 and R01 NS089777), N.S. (NIH U01 MH116488and R01 NS095654), S.K.M. (NIH R01 EY08411), and S.Q. (University of Arizona startup funds). We thank Dr. Haihui Xue (Hackensack University Medical Center) for providing the mouse Tle4 cDNA plasmid. We would like to acknowledge technical support and training from Benjamin Abrams in the UC Santa Cruz Life Sciences Microscopy Center. Use of the Zeiss 880 confocal microscope was made possible by the award of NIH S-10 Instrumentation grant 1S10OD23528-01. We would like to thank Ms. Hannah Maul-Newby and Dr. Melissa Jurica for technical assistance. We also thank our interns and volunteers that helped with the project, Cosmo Hahn, Hansen Lillemark, Emily Brumley, Litzy Rodriguez, Maanvi Thawani, and Sahiti Annadata. The graphical abstract was created with BioRender.com. B.C. J.T. D.T. Z.Y. S.Q. and S.K.M. designed all the experiments; J.T. D.T. X.M. A.N. T.F. L.H. G.L. D.G. A.M. J.M.R. and S.Q. performed all the experiments; N.S. provided resources and contributed to interpretation of the results; J.T. D.T. S.Q. and B.C. analyzed the data and wrote the manuscript; and S.K. analyzed the RNA-seq data. All authors read and edited the manuscript. The authors declare no competing interests. Funding Information: This study was supported by grants to B.C. ( NIH R01 MH094589 and R01 NS089777 ), N.S. ( NIH U01 MH116488 and R01 NS095654 ), S.K.M. ( NIH R01 EY08411 ), and S.Q. ( University of Arizona startup funds). We thank Dr. Haihui Xue (Hackensack University Medical Center) for providing the mouse Tle4 cDNA plasmid. We would like to acknowledge technical support and training from Benjamin Abrams in the UC Santa Cruz Life Sciences Microscopy Center. Use of the Zeiss 880 confocal microscope was made possible by the award of NIH S-10 Instrumentation grant 1S10OD23528-01 . We would like to thank Ms. Hannah Maul-Newby and Dr. Melissa Jurica for technical assistance. We also thank our interns and volunteers that helped with the project, Cosmo Hahn, Hansen Lillemark, Emily Brumley, Litzy Rodriguez, Maanvi Thawani, and Sahiti Annadata. The graphical abstract was created with BioRender.com . Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = jun,
day = "22",
doi = "10.1016/j.celrep.2021.109269",
language = "English (US)",
volume = "35",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",
}