Loss of Dmrt5 Affects the Formation of the Subplate and Early Corticogenesis

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 Ctip(2+) cortical neurons in Dmrt5(-/- )mice. In...

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Detalles Bibliográficos
Autores: Ratié, Leslie, Desmaris, Elodie, García Moreno, Fernando, Hoerder Suabedissen, Anna, Kelman, Alexandra, Theil, Thomas, Bellefroid, Eric J, Molnár, Zoltán
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/43927
Acceso en línea:http://hdl.handle.net/10810/43927
Access Level:acceso abierto
Palabra clave:corticogenesis
dmrt
neuronal migration
subplate cajal-retzius cells
radial glial-cells
white-matter
cerebral-cortex
developmental history
interstitial neurons
ganglionic eminence
postmitotic neurons
subventricular zone
Descripción
Sumario: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 Ctip(2+) 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 (Dmit5(lox/lox);Emx1(Cre)) but not late (Dmrt5(lox/lox);Nestin(Cre)) deletion of Dmrt5. SP was less disturbed in Dmrt5(lox/lox);Emx1(Cre) 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.