 |
 |
GEO help: Mouse over screen elements for information. |
|
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 |
Total RNA-seq from the cerebellum of SnoN conditional knockout and wildtype mice
|
|
|
Contributor(s) |
Chen X, Chanda A, Ikeuchi Y, Zhang X, VGoodman J, Reddy NC, Majidi SP, YWu D, 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 (6)
|
|
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 |
PRJNA492392 |
SRA |
SRP162303 |
Supplementary file |
Size |
Download |
File type/resource |
GSE120276_wholeCerebellum_P6_all.gene_counts.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
Raw data are available in SRA |
Processed data are available on Series record |
|
|
|
|
 |