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Series GSE120278 Query DataSets for GSE120278
Status Public on Dec 10, 2018
Title The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional knockout of the
transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal mouse brain. In laser capture microdissection followed by RNASeq, designed to profile gene expression specifically in the external granule layer (EGL) of the cerebellum, we find that SnoN promotes the expression of cell proliferation genes and concomitantly represses differentiation genes in granule neuron precursors in vivo. Remarkably,
bioinformatics analyses reveal that SnoN-regulated genes contain binding sites for the transcription factors N-myc and Pax6, which promote the proliferation and differentiation of granule neuron precursors, respectively. Accordingly, we uncover novel physical interactions of SnoN with N-myc and Pax6 in cells. In behavior analyses, conditional knockout of SnoN impairs cerebellar-dependent learning in a delayed eye-blink conditioning paradigm, suggesting that SnoN-regulation of granule neuron precursor proliferation bears functional consequences at the
organismal level. Our findings define a novel function and mechanism for the major transcriptional regulator SnoN in the control of granule neuron precursor proliferation in the mammalian brain.
 
Overall design We deployed a laser captured microdissection (lcm) approach to focus our analyses of SnoN specifically in the EGL of the developing mouse cerebellum. The transcriptome of laser captured microdissected EGL from conditional SnoN knockout and control littermate mice were were measured using RNA-seq.
 
Contributor(s) Chen X, Chanda A, Ikeuchi Y, Zhang X, Goodman JV, Reddy NC, Majidi SP, Wu DY, Smith SE, Godec A, Oldenborg A, Gabel HW, Zhao G, Bonni S, Bonni A
Citation(s) 30425119, 32600248
Submission date Sep 21, 2018
Last update date Jul 07, 2020
Contact name Guoyan Zhao
Organization name Washington University
Department Genetics & Neurology
Lab Guoyan Zhao
Street address 660 South Euclid Ave.
City St. Louis
State/province MO
ZIP/Postal code 63110
Country USA
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (12)
GSM3397498 EGLWT1
GSM3397499 EGLWT3
GSM3397500 EGLWT5
This SubSeries is part of SuperSeries:
GSE120279 The Transcriptional Regulator SnoN Promotes the Proliferation of Cerebellar Granule Neuron Precursors in the Postnatal Mouse Brain
Relations
BioProject PRJNA492391
SRA SRP162305

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Supplementary file Size Download File type/resource
GSE120278_RAW.tar 2.4 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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