E-GEOD-35260 - Functional dissection of the Paired domain of Pax6 – distinct roles of subdomains in neurogenesis and proliferation

Status
Released on 19 March 2013, last updated on 2 June 2014
Organism
Mus musculus
Samples (21)
Array (1)
Protocols (8)
Description
The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex. Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation. We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice
Experiment type
transcription profiling by array 
Contacts
Magdalena Goetz <magdalena.goetz@helmholtz-muenchen.de>, Ales Cvekl, Anastassia Stoykova, Dierk Nissing, Johannes Beckers, Jovica Ninkovic, Magdalena Götz, Martin Irmler, Qing Xie, Tessa Walcher
Citation
Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation. Walcher T, Xie Q, Sun J, Irmler M, Beckers J, Ozt�rk T, Niessing D, Stoykova A, Cvekl A, Ninkovic J, G�tz M. , Europe PMC 23404109
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-35260.idf.txt
Sample and data relationshipE-GEOD-35260.sdrf.txt
Raw data (1)E-GEOD-35260.raw.1.zip
Processed data (1)E-GEOD-35260.processed.1.zip
Array designA-AFFY-45.adf.txt
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