Negative-feedback regulation of proneural proteins controls the timing of neural precursor division

Pao Ju Chang, Yun Ling Hsiao, An Chi Tien, Yi Chen Li, Haiwei Pi*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations

Abstract

Neurogenesis requires precise control of cell specification and division. In Drosophila, the timing of cell division of the sensory organ precursor (SOP) is under strict temporal control. But how the timing of mitotic entry is determined remains poorly understood. Here, we present evidence that the timing of the G2-M transition is determined by when proneural proteins are degraded from SOPs. This process requires the E3 ubiquitin ligase complex, including the RING protein Sina and the adaptor Phyl. In phyl mutants, proneural proteins accumulate, causing delay or arrest in the G2-M transition. The G2-M defect in phyl mutants is rescued by reducing the ac and sc gene doses. Misexpression of phyl downregulates proneural protein levels in a sina-dependent manner. Phyl directly associates with proneural proteins to act as a bridge between proneural proteins and Sina. As phyl is a direct transcriptional target of Ac and Sc, our data suggest that, in addition to mediating cell cycle arrest, proneural protein initiates a negative-feedback regulation to time the mitotic entry of neural precursors.

Original languageEnglish
Pages (from-to)3021-3030
Number of pages10
JournalDevelopment (Cambridge)
Volume135
Issue number18
DOIs
StatePublished - 2008

Keywords

  • Degradation
  • Drosophila
  • Feedback
  • G2-M
  • Phyllopod
  • Proneural protein
  • Sina

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