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Series GSE35260 Query DataSets for GSE35260
Status Public on Mar 19, 2013
Title Functional dissection of the Paired domain of Pax6 – distinct roles of subdomains in neurogenesis and proliferation
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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.
 
Overall design We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice
 
Contributor(s) Walcher T, Xie Q, Beckers J, Nissing D, Irmler M, Stoykova A, Cvekl A, Ninkovic J, Götz M
Citation(s) 23404109
Submission date Jan 23, 2012
Last update date Feb 11, 2019
Contact name Johannes Beckers
E-mail(s) johannes.beckers@helmholtz-munich.de
Organization name Helmholtz Zentrum Muenchen
Department Institute of Experimental Genetics
Street address Ingolstaedter Landstr. 1
City Neuherberg
ZIP/Postal code 85764
Country Germany
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (21)
GSM864614 Pax6 mutant (Small-eye; Sey) rostral cerebral cortex at embryonic day E14, biological replicate 1
GSM864615 Pax6 mutant (Small-eye; Sey) rostral cerebral cortex at embryonic day E14, biological replicate 2
GSM864616 Pax6 mutant (Small-eye; Sey) rostral cerebral cortex at embryonic day E14, biological replicate 3
Relations
BioProject PRJNA152833

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE35260_RAW.tar 78.0 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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