par De Clercq, Sarah ; Keruzore, Marc ; Desmaris, Elodie ; Pollart, Charlotte ; Assimacopoulos, Stavroula; Preillon, Julie ; Ascenzo, Sabrina ; Matson, Clinton K; Lee, Melody M; Nakagawa, Yasushi; Hochepied, Tino; Zarkower, David; Grove, Elizabeth; Bellefroid, Eric
Référence Cerebral cortex, Advance Access, doi:10.1093/cercor/bhw384.
Publication Publié, 2016-12-27
Article révisé par les pairs
|Résumé :||Embryonic cerebral cortex patterning, which includes development of the neocortical area map, is critical to brain function, and only a few transcription factors have been demonstrated to control this process. The transcription factors Dmrt5/Dmrta2 and Dmrt3 are expressed in a similar graded manner in cortical progenitors. While DMRT5 has been thought to regulate cortical development indirectly, by promoting development of a critical signaling center in the cortical primordium, the cortical hem, the role of DMRT3 has not yet been addressed. By exploiting conditional gain- and loss-of-function Dmrt5 mouse models, we have generated bidirectional changes in the neocortical area map without affecting the hem, demonstrating that DMRT5 has a second, direct role in neocortical area patterning. Hippocampus development was also affected when DMRT5 was deleted after the hem had formed. Dmrt3 null mice show cortical patterning defects akin to but milder than those in Dmrt5 mutants, perhaps in part because Dmrt5 increases in the absence of Dmrt3. DMRT5 upregulates Dmrt3, and negatively autoregulates its expression. Together, our findings indicate that a finely tuned balance of DMRT5 and DMRT3 directly guide hippocampal development and neocortical area specification.|