Hoye et al. 2022 (PRJNA838490)

General Details

Title Identification of DDX3X-dependent translation targets in the E11.5 mouse cortex
Organism
Number of Samples 33
Release Date 2022/05/16 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP375353
ENA SRP375353
GEO
BioProject PRJNA838490

Publication

Title
Authors Hoye ML,Calviello L,Poff AJ,Ejimogu NE,Newman CR,Montgomery MD,Ou J,Floor SN,Silver DL
Journal eLife
Publication Date 2022 Jun 28
Abstract Mutations in the RNA helicase, DDX3X , are a leading cause of Intellectual Disability and present as DDX3X syndrome, a neurodevelopmental disorder associated with cortical malformations and autism. Yet, the cellular and molecular mechanisms by which DDX3X controls cortical development are largely unknown. Here, using a mouse model of Ddx3x loss-of-function we demonstrate that DDX3X directs translational and cell cycle control of neural progenitors, which underlies precise corticogenesis. First, we show brain development is sensitive to Ddx3x dosage; complete Ddx3x loss from neural progenitors causes microcephaly in females, whereas hemizygous males and heterozygous females show reduced neurogenesis without marked microcephaly. In addition, Ddx3x loss is sexually dimorphic, as its paralog, Ddx3y , compensates for Ddx3x in the developing male neocortex. Using live imaging of progenitors, we show that DDX3X promotes neuronal generation by regulating both cell cycle duration and neurogenic divisions. Finally, we use ribosome profiling in vivo to discover the repertoire of translated transcripts in neural progenitors, including those which are DDX3X-dependent and essential for neurogenesis. Our study reveals invaluable new insights into the etiology of DDX3X syndrome, implicating dysregulated progenitor cell cycle dynamics and translation as pathogenic mechanisms. © 2022, Hoye et al.
PMC PMC9239684
PMID 35762573
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR19217731 PRJNA838490 Mus musculus Ribo-Seq
SRR19217728 PRJNA838490 Mus musculus Ribo-Seq
SRR19217729 PRJNA838490 Mus musculus Ribo-Seq
SRR19217726 PRJNA838490 Mus musculus Ribo-Seq
SRR19217727 PRJNA838490 Mus musculus Ribo-Seq
SRR19217724 PRJNA838490 Mus musculus Ribo-Seq
SRR19217725 PRJNA838490 Mus musculus Ribo-Seq
SRR19217722 PRJNA838490 Mus musculus Ribo-Seq
SRR19217723 PRJNA838490 Mus musculus Ribo-Seq
SRR19217720 PRJNA838490 Mus musculus Ribo-Seq
SRR19217721 PRJNA838490 Mus musculus Ribo-Seq
SRR19217718 PRJNA838490 Mus musculus RNA-Seq
SRR19217719 PRJNA838490 Mus musculus RNA-Seq
SRR19217716 PRJNA838490 Mus musculus RNA-Seq
SRR19217717 PRJNA838490 Mus musculus RNA-Seq
SRR19217714 PRJNA838490 Mus musculus RNA-Seq
SRR19217715 PRJNA838490 Mus musculus RNA-Seq
SRR19217712 PRJNA838490 Mus musculus RNA-Seq
SRR19217713 PRJNA838490 Mus musculus RNA-Seq
SRR19217710 PRJNA838490 Mus musculus RNA-Seq
SRR19217711 PRJNA838490 Mus musculus RNA-Seq
SRR19217708 PRJNA838490 Mus musculus RNA-Seq
SRR19217709 PRJNA838490 Mus musculus Ribo-Seq
SRR19217706 PRJNA838490 Mus musculus Ribo-Seq
SRR19217707 PRJNA838490 Mus musculus Ribo-Seq
SRR19217704 PRJNA838490 Mus musculus Ribo-Seq
SRR19217705 PRJNA838490 Mus musculus Ribo-Seq
SRR19217702 PRJNA838490 Mus musculus Ribo-Seq
SRR19217703 PRJNA838490 Mus musculus Ribo-Seq
SRR19217700 PRJNA838490 Mus musculus Ribo-Seq
SRR19217701 PRJNA838490 Mus musculus Ribo-Seq
SRR19217698 PRJNA838490 Mus musculus Ribo-Seq
SRR19217699 PRJNA838490 Mus musculus Ribo-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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