Dataset Information


Minor spliceosome inactivation in the developing mouse cortex causes self-amplifying radial glial cell death and microcephaly.

ABSTRACT: Inactivation of the minor spliceosome has been linked to microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). To interrogate how minor intron splicing regulates cortical development, we employed Emx1-Cre to ablate Rnu11, which encodes the minor spliceosome-specific U11 small nuclear RNA (snRNA), in the developing cortex (pallium). Rnu11 cKO mice were born with microcephaly, caused by death of self-amplifying radial glial cells (RGCs). However, both intermediate progenitor cells (IPCs) and neurons were produced in the U11-null pallium. RNAseq of the pallium revealed elevated minor intron retention in the mutant, particularly in genes regulating cell cycle. Moreover, the only downregulated minor intron-containing gene (MIG) was Spc24, which regulates kinetochore assembly. These findings were consistent with the observation of fewer RGCs entering cytokinesis prior to RGC loss, underscoring the requirement of minor splicing for cell cycle progression in RGCs. Overall, we provide a potential explanation of how disruption of minor splicing might cause microcephaly in MOPD1. Overall design: RNA-seq on 5 control and 5 U11 mutant E12 dorsal telencephalon.

INSTRUMENT(S): Illumina NextSeq 500 (Mus musculus)

SUBMITTER: Rahul N Kanadia  

PROVIDER: GSE96616 | GEO | 2018-06-05


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Minor spliceosome inactivation causes microcephaly, owing to cell cycle defects and death of self-amplifying radial glial cells.

Baumgartner Marybeth M   Olthof Anouk M AM   Aquino Gabriela S GS   Hyatt Katery C KC   Lemoine Christopher C   Drake Kyle K   Sturrock Nikita N   Nguyen Nhut N   Al Seesi Sahar S   Kanadia Rahul N RN  

Development (Cambridge, England) 20180828 17

Mutation in minor spliceosome components is linked to the developmental disorder microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Here, we inactivated the minor spliceosome in the developing mouse cortex (pallium) by ablating Rnu11, which encodes the crucial minor spliceosome small nuclear RNA (snRNA) U11. Rnu11 conditional knockout mice were born with microcephaly, which was caused by the death of self-amplifying radial glial cells (RGCs), while intermediate progenitor cells an  ...[more]

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