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Fate Specification and Tissue-specific Cell Cycle Control of the Caenorhabditis elegans Intestine
Authors:Alexandra Segref  Juan Cabello  Caroline Clucas  Ralf Schnabel  Iain L. Johnstone
Affiliation:*Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom; ;Oncology Area, Centre for Biomedical Research of La Rioja, 26006 Logrono, Spain; and ;§Institut für Genetik, TU Braunschweig, 38106 Braunschweig, Germany
Abstract:Coordination between cell fate specification and cell cycle control in multicellular organisms is essential to regulate cell numbers in tissues and organs during development, and its failure may lead to oncogenesis. In mammalian cells, as part of a general cell cycle checkpoint mechanism, the F-box protein β-transducin repeat-containing protein (β-TrCP) and the Skp1/Cul1/F-box complex control the periodic cell cycle fluctuations in abundance of the CDC25A and B phosphatases. Here, we find that the Caenorhabditis elegans β-TrCP orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over several embryonic cell cycles and specifies cell number of one tissue, the embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may be developmentally controlled because CDC-25.1 accumulates over time within the developing germline, where LIN-23 is also present. Concurrent with the destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant.
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