4.6 Article

The Doublesex Homolog Dmrt5 is Required for the Development of the Caudomedial Cerebral Cortex in Mammals

期刊

CEREBRAL CORTEX
卷 23, 期 11, 页码 2552-2567

出版社

OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhs234

关键词

choroid plexus; cortical hem; Emx2; telencephalon; Wnt; Bmp

资金

  1. Belgian Fonds de la Recherche Scientifique [FRFC 3.4635.06]
  2. Belgian Queen Elisabeth Medical Foundation
  3. Federation Wallonie-Bruxelles (Action de Recherche Concertee)
  4. Interuniversity Attraction Poles Programme, Belgian State, Federal Office for Scientific, Technical and Cultural Affairs [IUAP-P5/35]
  5. Walloon Region Excellence Programme (CIBLES)
  6. Medical Research Council [G0801359]
  7. US National Institute of health [GM059152]
  8. US National Science Foundation
  9. Belgian Fonds de la Recherche Scientifique (Fonds pour la formation a la Recherche dans l'Industrie et dans l'Agriculture)
  10. Medical Research Council [G0801359] Funding Source: researchfish
  11. MRC [G0801359] Funding Source: UKRI

向作者/读者索取更多资源

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 CajalRetzius 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.

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