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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 16, 2010 |
| Title |
Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The morphogen and mitogen, Sonic Hedgehog, activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNPs) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Sonic Hedgehog signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of naïve mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Sonic Hedgehog signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Sonic Hedgehog-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborates with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development.
Keywords: disease state analysis
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| Overall design |
14 samples, 1 time series, 2 engineered Medulloblastoma tumors
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| Contributor(s) |
Ayrault O, Zhao H, Zindy F, Qu C, Sherr CJ, Roussel MF |
| Citation(s) |
20516124 |
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| Submission date |
Dec 28, 2009 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Chunxu Qu |
| E-mail(s) |
chunxu.qu@stjude.org
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| Phone |
9015952433
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| Organization name |
St Jude Children's Research Institute
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| Department |
Pathology
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| Lab |
Mullighan
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| Street address |
262 Danny Thomas Pl
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (14)
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| GSM491501 |
GNPs expressing Math1-ER treated with Tamoxifen for 8 hours |
| GSM491502 |
GNPs expressing Math1-ER treated with Tamoxifen for 24 hours |
| GSM491503 |
GNPs expressing Math1-ER treated with Tamoxifen for 4 hours |
| GSM491504 |
GNPs expressing Math1-ER with no Tamoxifen treatment |
| GSM491505 |
GNPs expressing Math1 DNA-binding mutant treated with Tamoxifen for 4 hours |
| GSM491506 |
Gli1 engineered Medulloblastoma, biological replicate 1 |
| GSM491507 |
Gli1 engineered Medulloblastoma, biological replicate 2 |
| GSM491508 |
Gli1 engineered Medulloblastoma, biological replicate 3 |
| GSM491509 |
Atoh1 engineered Medulloblastoma, biological replicate 1 |
| GSM491510 |
Atoh1 engineered Medulloblastoma, biological replicate 2 |
| GSM491511 |
Atoh1 engineered Medulloblastoma, biological replicate 3 |
| GSM491516 |
granule neuron precursors, biological replicate 1 |
| GSM491517 |
granule neuron precursors, biological replicate 2 |
| GSM491518 |
granule neuron precursors, biological replicate 3 |
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| Relations |
| BioProject |
PRJNA122515 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19684_RAW.tar |
51.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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