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Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon.

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Author

  • Pontus Holm
  • Michael T Mader
  • Nicole Haubst
  • Andrea Wizenmann
  • Mikael Sigvardsson
  • Magdalena Gotz

Summary, in English

Appropriate neurogenesis and patterning of the forebrain requires the transcription factor Pax6, yet it is largely unknown how Pax6 exerts its effects at the molecular level. To characterize Pax6-mediated regulation of gene expression during murine forebrain neurogenesis, we performed microarray analysis with tissue from the dorsal Pax6-dependent telencephalon and the ventral Pax6-negative telencephalon at the onset of neurogenesis (E12) and at mid-neurogenesis (E15) in wild-type and Pax6-deficient mutant littermates. In the Pax6-deficient cortex the expression levels of various transcription factors involved in neurogenesis (like Satb2, Nfia, AP-2 gamma, NeuroD6, Ngn2, Tbr2, Bhlhb5) and the retinoic acid signalling molecule Rlbp1 were reduced. Regulation by Pax6 could be confirmed upon electroporation of a Pax6- and a dominant-negative Pax6-containing vector into embryonic cortex. Taken together, our data reveal novel insights into the molecular pathways regulated by Pax6 during cortical neurogenesis. Most intriguingly, this analysis revealed time- and region-specific differences in Pax6-mediated transcription, explaining the specific function of Pax6 at early and later stages of neurogenesis. (c) 2006 Elsevier Inc. All rights reserved.

Department/s

Publishing year

2007

Language

English

Pages

99-119

Publication/Series

Molecular and Cellular Neuroscience

Volume

34

Issue

1

Document type

Journal article review

Publisher

Elsevier

Topic

  • Other Clinical Medicine
  • Cell and Molecular Biology

Keywords

  • neurogenesis
  • retinoic acid signalling
  • electroporation
  • cortex
  • Pax6
  • microarray
  • telencephalon
  • ganglionic eminence
  • small eye

Status

Published

ISBN/ISSN/Other

  • ISSN: 1044-7431