Loss of Dmrt5 affects the formation of the subplate and early corticogenesis

Leslie Ratié, Elodie Desmaris, Fernando García-Moreno, Anna Hoerder-Suabedissen, Alexandra Kelman, Thomas Theil, Eric J Bellefroid, Zoltan Molnar

Research output: Contribution to journalArticlepeer-review

Abstract

Dmrt5 (Dmrta2) and Dmrt3 are key regulators of cortical patterning and progenitor proliferation and differentiation. In this study, we show an altered apical to intermediate progenitor transition, with a delay in SP neurogenesis and premature birth of Ctip2+ cortical neurons in Dmrt5−/− mice. In addition to the cortical progenitors, DMRT5 protein appears present in postmitotic subplate (SP) and marginal zone neurons together with some migrating cortical neurons. We observed the altered split of preplate and the reduced SP and disturbed radial migration of cortical neurons into cortical plate in Dmrt5−/−brains and demonstrated an increase in the proportion of multipolar cells in primary neuronal cultures from Dmrt5−/−embryonic brains. Dmrt5 affects cortical development with specific time sensitivity that we described in two conditional mice with slightly different deletion time. We only observed a transient SP phenotype at E15.5, but not by E18.5 after early (Dmrt5lox/lox;Emx1Cre), but not late (Dmrt5lox/lox;NestinCre) deletion of Dmrt5. SP was less disturbed in Dmrt5lox/lox;Emx1Cre and Dmrt3−/− brains than in Dmrt5−/− and affects dorsomedial cortex more than lateral and caudal cortex. Our study demonstrates a novel function of Dmrt5 in the regulation of early SP formation and radial cortical neuron migration.
Original languageEnglish
Pages (from-to)3296–3312
Number of pages17
JournalCerebral Cortex
Volume30
Issue number5
Early online date16 Dec 2019
DOIs
Publication statusPublished - 31 May 2020

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