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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 04, 2010 |
| Title |
Expression profiling analysis of mouse E10.5 Magoh mutant brain cortices |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Human brain structure and size requires regulated division of neural stem cells (NSCs). NSCs undergo precise divisions to self-renew and to produce intermediate neural progenitors (INPs) and neurons. The factors that regulate NSC divisions remain poorly understood, as do mechanistic explanations of how aberrant NSC division causes reduced brain size, as seen in microcephaly. Here we demonstrate that Magoh, a component of the core exon junction complex (EJC) that binds spliced RNA, controls cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly due to INP depletion, neuronal apoptosis, and improper mitotic spindle orientation. Defective mitosis underlies these phenotypes as depletion of EJC components disrupts mitotic spindle integrity, chromosome number and genomic stability. We show that an essential function of Magoh is to regulate expression of the human microcephaly protein, LIS1, and that Lis1 addition rescues neurogenesis defects caused by Magoh knockdown, thus providing a genetic explanation for the microcephaly. This study uncovers new requirements for the EJC in brain development, NSC maintenance, mitosis and chromosome stability, thus implicating this complex in the pathogenesis of microcephaly.
Mouse embryonic cortices were used for expression analysis
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| Overall design |
5 biological replicates each of control (C57BL/6) and Magoh mutant brains were analyzed
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| Contributor(s) |
Silver DL, Watkins-Chow DE, Schreck KC, Pierfelice TJ, Larson DM, Burnetti AJ, Liaw H, Myung K, Walsh CA, Gaiano N, Pavan WJ |
| Citation(s) |
20364144 |
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| Submission date |
Nov 24, 2009 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Christopher Pan |
| E-mail(s) |
[email protected]
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| Organization name |
NIH
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| Department |
NHGRI
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| Street address |
Rm 5228, Bldg 50, South Dr.
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (10)
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| GSM475265 |
E10.5 wild-type cortex, biological rep 1 |
| GSM475266 |
E10.5 wild-type cortex, biological rep 2 |
| GSM475267 |
E10.5 wild-type cortex, biological rep 3 |
| GSM475268 |
E10.5 wild-type cortex, biological rep 4 |
| GSM475269 |
E10.5 wild-type cortex, biological rep 5 |
| GSM475270 |
E10.5 Magoh mutant cortex, biological rep 1 |
| GSM475271 |
E10.5 Magoh mutant cortex, biological rep 2 |
| GSM475272 |
E10.5 Magoh mutant cortex, biological rep 3 |
| GSM475273 |
E10.5 Magoh mutant cortex, biological rep 4 |
| GSM475274 |
E10.5 Magoh mutant cortex, biological rep 5 |
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| Relations |
| BioProject |
PRJNA120731 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19168_GeneSifter_RMA_processed_data.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| GSE19168_RAW.tar |
44.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data provided as supplementary file |
| Processed data included within Sample table |
| Processed data are available on Series record |
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