The COMPASS Family Protein ASH2L Mediates Corticogenesis via Transcriptional Regulation of Wnt Signaling.
Cell Rep
; 28(3): 698-711.e5, 2019 07 16.
Article
en En
| MEDLINE
| ID: mdl-31315048
ABSTRACT
Histone methylation is essential for regulating gene expression during organogenesis to maintain stem cells and execute a proper differentiation program for their descendants. Here we show that the COMPASS family histone methyltransferase co-factor ASH2L is required for maintaining neural progenitor cells (NPCs) and the production and positioning of projection neurons during neocortex development. Specifically, loss of Ash2l in NPCs results in malformation of the neocortex; the mutant neocortex has fewer neurons, which are also abnormal in composition and laminar position. Moreover, ASH2L loss impairs trimethylation of H3K4 and the transcriptional machinery specific for Wnt-ß-catenin signaling, inhibiting the proliferation ability of NPCs at late stages of neurogenesis by disrupting S phase entry to inhibit cell cycle progression. Overexpressing ß-catenin after ASH2L elimination rescues the proliferation deficiency. Therefore, our findings demonstrate that ASH2L is crucial for modulating Wnt signaling to maintain NPCs and generate a full complement of neurons during mammalian neocortex development.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Neocórtex
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Proteínas de Unión al ADN
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Neurogénesis
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Células-Madre Neurales
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Vía de Señalización Wnt
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2019
Tipo del documento:
Article