title: Cyclin E and CDK-2 regulate proliferative cell fate and cell cycle progression in the C. elegans germline.
abstract: The C. elegans germline provides an excellent model for analyzing the regulation of stem cell activity and the decision to differentiate and undergo meiotic development. The distal end of the adult hermaphrodite germline contains the proliferative zone, which includes a population of mitotically cycling cells and cells in meiotic S phase, followed by entry into meiotic prophase. The proliferative fate is specified by somatic distal tip cell (DTC) niche-germline GLP-1 Notch signaling through repression of the redundant GLD-1 and GLD-2 pathways that promote entry into meiosis. Here, we describe characteristics of the proliferative zone, including cell cycle kinetics and population dynamics, as well as the role of specific cell cycle factors in both cell cycle progression and the decision between the proliferative and meiotic cell fate. Mitotic cell cycle progression occurs rapidly, continuously, with little or no time spent in G1, and with cyclin E (CYE-1) levels and activity high throughout the cell cycle. In addition to driving mitotic cell cycle progression, CYE-1 and CDK-2 also play an important role in proliferative fate specification. Genetic analysis indicates that CYE-1/CDK-2 promotes the proliferative fate downstream or in parallel to the GLD-1 and GLD-2 pathways, and is important under conditions of reduced GLP-1 signaling, possibly corresponding to mitotically cycling proliferative zone cells that are displaced from the DTC niche. Furthermore, we find that GLP-1 signaling regulates a third pathway, in addition to the GLD-1 and GLD-2 pathways and also independent of CYE-1/CDK-2, to promote the proliferative fate/inhibit meiotic entry.
authors.affiliation: Department of Genetics, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Fox
authors.forename: Valarie E
authors.initials: VE
authors.lastname: Vought
authors.forename: Momoyo
authors.initials: M
authors.lastname: Hanazawa
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Lee
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Maine
authors.forename: Tim
authors.initials: T
authors.lastname: Schedl
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D011062:Polynucleotide Adenylyltransferase / Q000378:metabolism; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D013234:Stem Cells
chemical_list: D029742:Caenorhabditis elegans Proteins; D019927:Cyclin E; C094448:GLD-1 protein, C elegans; C060620:Glp-1 protein, C elegans; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D051357:Cyclin-Dependent Kinase 2; C491056:GLD-2 protein, C elegans; D011062:Polynucleotide Adenylyltransferase