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  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., Öztürk, T., et al. (2013). Functional dissection of the paired domain of Pax6 reveals molecular mechanisms of coordinating neurogenesis and proliferation. Development, 140(5), 1123-1136. doi:10.1242/dev.082875.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-B7CE-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0018-DB09-E
Genre: Journal Article

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 Creators:
Walcher, T., Author
Xie, Q., Author
Sun, J., Author
Irmler, M., Author
Beckers, J., Author
Öztürk, T., Author
Niessing, D., Author
Stoykova, A.1, Author              
Cvekl, A., Author
Ninkovic, J., Author
Götz, M., Author
Affiliations:
1Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578587              

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Free keywords: Transcriptional regulator, Radial glia, Cortex development, Mouse
 Abstract: To achieve adequate organ development and size, cell proliferation and differentiation have to be tightly regulated and coordinated. The transcription factor Pax6 regulates patterning, neurogenesis and proliferation in forebrain development. The molecular basis of this regulation is not well understood. As the bipartite DNA-binding paired domain of Pax6 regulates forebrain development, we examined mice with point mutations in its individual DNA-binding subdomains PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C). This revealed distinct roles in regulating proliferation in the developing cerebral cortex, with the PAI and RED subdomain mutations reducing and increasing, respectively, the number of mitoses. Conversely, neurogenesis was affected only by the PAI subdomain mutation, phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression profiling identified molecularly discrete signatures of Pax6Leca4 and Pax6Leca2 mutations. Comparison to Pax6 targets identified by chromatin immunoprecipitation led to the identification and functional characterization of distinct DNA motifs in the promoters of target genes dysregulated in the Pax6Leca2 or Pax6Leca4 mutants, further supporting the distinct regulatory functions of the DNA-binding subdomains. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing particular subdomains to coordinate patterning, neurogenesis and proliferation simultaneously.

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Language(s): eng - English
 Dates: 2013-03-012013
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1242/dev.082875
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Title: Development
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Source Genre: Journal
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Publ. Info: Cambridge, Cambridgeshire : Company of Biologists
Pages: - Volume / Issue: 140 (5) Sequence Number: - Start / End Page: 1123 - 1136 Identifier: ISSN: 0950-1991
CoNE: https://pure.mpg.de/cone/journals/resource/954927546241