title: The doublesex homolog Dmrt5 is required for the development of the caudomedial cerebral cortex in mammals.
abstract: Regional patterning of the cerebral cortex is initiated by morphogens secreted by patterning centers that establish graded expression of transcription factors within cortical progenitors. Here, we show that Dmrt5 is expressed in cortical progenitors in a high-caudomedial to low-rostrolateral gradient. In its absence, the cortex is strongly reduced and exhibits severe abnormalities, including agenesis of the hippocampus and choroid plexus and defects in commissural and thalamocortical tracts. Loss of Dmrt5 results in decreased Wnt and Bmp in one of the major telencephalic patterning centers, the dorsomedial telencephalon, and in a reduction of Cajal-Retzius cells. Expression of the dorsal midline signaling center-dependent transcription factors is downregulated, including Emx2, which promotes caudomedial fates, while the rostral determinant Pax6, which is inhibited by midline signals, is upregulated. Consistently, Dmrt5(-/-) brains exhibit patterning defects with a dramatic reduction of the caudomedial cortex. Dmrt5 is increased upon the activation of Wnt signaling and downregulated in Gli3(xt/xt) mutants. We conclude that Dmrt5 is a novel Wnt-dependent transcription factor required for early cortical development and that it may regulate initial cortical patterning by promoting dorsal midline signaling center formation and thereby helping to establish the graded expression of the other transcription regulators of cortical identity.
authors.affiliation: Laboratoire de Génétique du Développement, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires (IBMM), Gosselies, Belgium.
authors.forename: Amandine
authors.initials: A
authors.lastname: Saulnier
authors.forename: Marc
authors.initials: M
authors.lastname: Keruzore
authors.forename: Sarah
authors.initials: S
authors.lastname: De Clercq
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bar
authors.forename: Virginie
authors.initials: V
authors.lastname: Moers
authors.forename: Dario
authors.initials: D
authors.lastname: Magnani
authors.forename: Tessa
authors.initials: T
authors.lastname: Walcher
authors.forename: Carol
authors.initials: C
authors.lastname: Filippis
authors.forename: Sadia
authors.initials: S
authors.lastname: Kricha
authors.forename: Damien
authors.initials: D
authors.lastname: Parlier
authors.forename: Laurène
authors.initials: L
authors.lastname: Viviani
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Matson
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Thomas
authors.initials: T
authors.lastname: Theil
authors.forename: Magdalena
authors.initials: M
authors.lastname: Götz
authors.forename: Antonello
authors.initials: A
authors.lastname: Mallamaci
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Marine
authors.forename: David
authors.initials: D
authors.lastname: Zarkower
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bellefroid
mesh_terms: D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D051153:Wnt Proteins; C560422:mab-3-related transcription factor 5, mouse; D052004:Bone Morphogenetic Protein Receptors