QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deng, W.-M. Articles by Ruohola-Baker, H. Search for Related Content PubMed PubMed Citation Articles by Deng, W.-M. Articles by Ruohola-Baker, H.

Notch-Delta signaling induces a transition from mitotic cell cycle to endocycle in Drosophila follicle cells

Department of Biochemistry, University of Washington, J591, HSB, Seattle, WA 98195-7350, USA

*Author for correspondence (e-mail: hannele{at}u.washington.edu)

Accepted August 23, 2001

In many developmental processes, polyploid cells are generated by a variation of the normal cell cycle called the endocycle in which cells increase their genomic content without dividing. How the transition from the normal mitotic cycle to endocycle is regulated is poorly understood. We show that the transition from mitotic cycle to endocycle in the Drosophila follicle cell epithelium is regulated by the Notch pathway. Loss of Notch function in follicle cells or its ligand Delta function in the underlying germline disrupts the normal transition of the follicle cells from mitotic cycle to endocycle, mitotic cycling continues, leading to overproliferation of these cells. The regulation is at the transcriptional level, as Su(H), a downstream transcription factor in the pathway, is also required cell autonomously in follicle cells for proper transitioning to the endocycle. One target of Notch and Su(H) is likely to be the G2/M cell cycle regulator String, a phosphatase that activates Cdc2 by dephosphorylation. String is normally repressed in the follicle cells just before the endocycle transition, but is expressed when Notch is inactivated. Analysis of the activity of String enhancer elements in follicle cells reveals the presence of an element that promotes expression of String until just before the onset of polyploidy in wild-type follicle cells but well beyond this stage in Notch mutant follicle cells. This suggests that it may be the target of the endocycle promoting activity of the Notch pathway. A second element that is insensitive to Notch regulation promotes String expression earlier in follicle cell development, which explains why Notch, while active at both stages, represses String only at the mitotic cycle-endocycle transition.

Key words: Drosophila, Notch, Delta, Cell cycle, Follicle cells

This article has been cited by other articles:

				J. Sun, L. Smith, A. Armento, and W.-M. Deng Regulation of the endocycle/gene amplification switch by Notch and ecdysone signaling J. Cell Biol., September 8, 2008; 182(5): 885 - 896. [Abstract] [Full Text] [PDF]

				X. Wu, M. Yamada-Mabuchi, E. J. Morris, P. S. Tanwar, L. Dobens, S. Gluderer, S. Khan, J. Cao, H. Stocker, E. Hafen, et al. The Drosophila homolog of human tumor suppressor TSC-22 promotes cellular growth, proliferation, and survival PNAS, April 8, 2008; 105(14): 5414 - 5419. [Abstract] [Full Text] [PDF]

				T. Vaccari, H. Lu, R. Kanwar, M. E. Fortini, and D. Bilder Endosomal entry regulates Notch receptor activation in Drosophila melanogaster J. Cell Biol., February 25, 2008; 180(4): 755 - 762. [Abstract] [Full Text] [PDF]

				B. R. Calvi, B. A. Byrnes, and A. J. Kolpakas Conservation of Epigenetic Regulation, ORC Binding and Developmental Timing of DNA Replication Origins in the Genus Drosophila Genetics, November 1, 2007; 177(3): 1291 - 1301. [Abstract] [Full Text] [PDF]

				C. L. Curry, L. L. Reed, E. Broude, T. E. Golde, L. Miele, and K. E. Foreman Notch inhibition in Kaposi's sarcoma tumor cells leads to mitotic catastrophe through nuclear factor-{kappa}B signaling Mol. Cancer Ther., July 1, 2007; 6(7): 1983 - 1992. [Abstract] [Full Text] [PDF]

				M. Grammont Adherens junction remodeling by the Notch pathway in Drosophila melanogaster oogenesis J. Cell Biol., April 9, 2007; 177(1): 139 - 150. [Abstract] [Full Text] [PDF]

				M. Schneider, A. A. Khalil, J. Poulton, C. Castillejo-Lopez, D. Egger-Adam, A. Wodarz, W.-M. Deng, and S. Baumgartner Perlecan and Dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization Development, October 1, 2006; 133(19): 3805 - 3815. [Abstract] [Full Text] [PDF]

				A. M. O'Reilly, A. C. Ballew, B. Miyazawa, H. Stocker, E. Hafen, and M. A. Simon Csk differentially regulates Src64 during distinct morphological events in Drosophila germ cells Development, July 15, 2006; 133(14): 2627 - 2638. [Abstract] [Full Text] [PDF]

				J. Sun and W.-M. Deng Notch-dependent downregulation of the homeodomain gene cut is required for the mitotic cycle/endocycle switch and cell differentiation in Drosophila follicle cells Development, October 1, 2005; 132(19): 4299 - 4308. [Abstract] [Full Text] [PDF]

				J. C. Adam and D. J. Montell A role for extra macrochaetae downstream of Notch in follicle cell differentiation Development, December 1, 2004; 131(23): 5971 - 5980. [Abstract] [Full Text] [PDF]

				H. R. Shcherbata, C. Althauser, S. D. Findley, and H. Ruohola-Baker The mitotic-to-endocycle switch in Drosophila follicle cells is executed by Notch-dependent regulation of G1/S, G2/M and M/G1 cell-cycle transitions Development, July 1, 2004; 131(13): 3169 - 3181. [Abstract] [Full Text] [PDF]

				J. Z. Maines, L. M. Stevens, X. Tong, and D. Stein Drosophila dMyc is required for ovary cell growth and endoreplication Development, February 15, 2004; 131(4): 775 - 786. [Abstract] [Full Text] [PDF]

				P. Cayirlioglu, W. O. Ward, S. C. Silver Key, and R. J. Duronio Transcriptional Repressor Functions of Drosophila E2F1 and E2F2 Cooperate To Inhibit Genomic DNA Synthesis in Ovarian Follicle Cells Mol. Cell. Biol., March 15, 2003; 23(6): 2123 - 2134. [Abstract] [Full Text] [PDF]

				M. Grammont and K. D. Irvine Organizer activity of the polar cells during Drosophila oogenesis Development, March 13, 2003; 129(22): 5131 - 5140. [Abstract] [Full Text] [PDF]

				W.-M. Deng, M. Schneider, R. Frock, C. Castillejo-Lopez, E. A. Gaman, S. Baumgartner, and H. Ruohola-Baker Dystroglycan is required for polarizing the epithelial cells and the oocyte in Drosophila Development, January 1, 2003; 130(1): 173 - 184. [Abstract] [Full Text] [PDF]

				J. Bai and D. Montell Eyes Absent, a key repressor of polar cell fate during Drosophila oogenesis Development, January 12, 2002; 129(23): 5377 - 5388. [Abstract] [Full Text] [PDF]

				J. E. Smith III, C. A. Cummings, and C. Cronmiller daughterless coordinates somatic cell proliferation, differentiation and germline cyst survival during follicle formation in Drosophila Development, January 7, 2002; 129(13): 3255 - 3267. [Abstract] [Full Text] [PDF]

				J. R. McGregor, R. Xi, and D. A. Harrison JAK signaling is somatically required for follicle cell differentiation in Drosophila Development, January 2, 2002; 129(3): 705 - 717. [Abstract] [Full Text] [PDF]