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First published online 13 August 2008
doi: 10.1242/dev.021923

Development 135, 3021-3030 (2008)
Published by The Company of Biologists 2008
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Negative-feedback regulation of proneural proteins controls the timing of neural precursor division

Pao-Ju Chang1,*, Yun-Ling Hsiao1,*, An-Chi Tien2, Yi-Chen Li1 and Haiwei Pi1,{dagger}

1 Department of Life Science, Chang-Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan.
2 Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

{dagger} Author for correspondence (e-mail: haiwei{at}mail.cgu.edu.tw)

Accepted 1 July 2008

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.

Key words: Proneural protein, Feedback, G2-M, Phyllopod, Sina, Degradation, Drosophila


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Related articles in Development:

Proneural proteins keep mitotic time

Development 2008 135: e1803. [Full Text]  



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Home page
 J. Cell Sci.Home page
P.-J. Chang, Y.-L. Hsiao, A.-C. Tien, Y.-C. Li, and H. Pi
Negative-feedback regulation of proneural proteins controls the timing of neural precursor division
J. Cell Sci., September 15, 2008; 121(18): e1806 - e1806.
[Full Text]


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