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

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Abstract

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.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Other Clinical Medicine
  • Cell and Molecular Biology

Keywords

  • neurogenesis, retinoic acid signalling, electroporation, cortex, Pax6, microarray, telencephalon, ganglionic eminence, small eye
Original languageEnglish
Pages (from-to)99-119
JournalMolecular and Cellular Neuroscience
Volume34
Issue number1
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes