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Publication : TBR1 directly represses Fezf2 to control the laminar origin and development of the corticospinal tract.

First Author  Han W Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  7 Pages  3041-6
PubMed ID  21285371 Mgi Jnum  J:169221
Mgi Id  MGI:4940125 Doi  10.1073/pnas.1016723108
Citation  Han W, et al. (2011) TBR1 directly represses Fezf2 to control the laminar origin and development of the corticospinal tract. Proc Natl Acad Sci U S A 108(7):3041-6
abstractText  The corticospinal (CS) tract is involved in controlling discrete voluntary skilled movements in mammals. The CS tract arises exclusively from layer (L) 5 projection neurons of the cerebral cortex, and its formation requires L5 activity of Fezf2 (Fezl, Zfp312). How this L5-specific pattern of Fezf2 expression and CS axonal connectivity is established with such remarkable fidelity had remained elusive. Here we show that the transcription factor TBR1 directly binds the Fezf2 locus and represses its activity in L6 corticothalamic projection neurons to restrict the origin of the CS tract to L5. In Tbr1 null mutants, CS axons ectopically originate from L6 neurons in a Fezf2-dependent manner. Consistently, misexpression of Tbr1 in L5 CS neurons suppresses Fezf2 expression and effectively abolishes the CS tract. Taken together, our findings show that TBR1 is a direct transcriptional repressor of Fezf2 and a negative regulator of CS tract formation that restricts the laminar origin of CS axons specifically to L5.
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