title: DMRT5 Together with DMRT3 Directly Controls Hippocampus Development and Neocortical Area Map Formation.
abstract: Mice that are constitutively null for the zinc finger doublesex and mab-3 related (Dmrt) gene, Dmrt5/Dmrta2, show a variety of patterning abnormalities in the cerebral cortex, including the loss of the cortical hem, a powerful cortical signaling center. In conditional Dmrt5 gain of function and loss of function mouse models, we generated bidirectional changes in the neocortical area map without affecting the hem. Analysis indicated that DMRT5, independent of the hem, directs the rostral-to-caudal pattern of the neocortical area map. Thus, DMRT5 joins a small number of transcription factors shown to control directly area size and position in the neocortex. Dmrt5 deletion after hem formation also reduced hippocampal size and shifted the position of the neocortical/paleocortical boundary. Dmrt3, like Dmrt5, is expressed in a gradient across the cortical primordium. Mice lacking Dmrt3 show cortical patterning defects akin to but milder than those in Dmrt5 mutants, perhaps in part because Dmrt5 expression increases in the absence of Dmrt3. DMRT5 upregulates Dmrt3 expression and negatively regulates its own expression, which may stabilize the level of DMRT5. Together, our findings indicate that finely tuned levels of DMRT5, together with DMRT3, regulate patterning of the cerebral cortex.
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: De Clercq
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Keruzore
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Elodie
authors.initials: E
authors.lastname: Desmaris
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Pollart
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Assimacopoulos
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Preillon
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ascenzo
authors.affiliation: Department of Genetics, Cell Biology and Development , Minneapolis, MN 55455, USA.
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Matson
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Melody
authors.initials: M
authors.lastname: Lee
authors.affiliation: School of Medicine and School of Bioscience , Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, CF10 3XQ, UK.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Nan
authors.affiliation: School of Medicine and School of Bioscience , Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, CF10 3XQ, UK.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium.|Inflammation Research Center, VIB, B-9052 Ghent, Belgium.
authors.forename: Tino
authors.initials: T
authors.lastname: Hochepied
authors.affiliation: Department of Genetics, Cell Biology and Development , Minneapolis, MN 55455, USA.
authors.forename: David
authors.initials: D
authors.lastname: Zarkower
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grove
authors.affiliation: ULB Institute of Neuroscience (UNI), Université Libre de Bruxelles (ULB), B-6041 Gosselies, Belgium.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bellefroid
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019579:Neocortex / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: C473014:Dmrt3 protein, mouse; D014157:Transcription Factors; C560422:mab-3-related transcription factor 5, mouse
keywords: cortical hem; hippocampus; neocortex; neocortical area map; transcription factor