title: Regulation of the endocycle/gene amplification switch by Notch and ecdysone signaling.
abstract: The developmental signals that regulate the switch from genome-wide DNA replication to site-specific amplification remain largely unknown. Drosophila melanogaster epithelial follicle cells, which begin synchronized chorion gene amplification after three rounds of endocycle, provide an excellent model for study of the endocycle/gene amplification (E/A) switch. Here, we report that down-regulation of Notch signaling and activation of ecdysone receptor (EcR) are required for the E/A switch in these cells. Extended Notch activity suppresses EcR activation and prevents exit from the endocycle. Tramtrack (Ttk), a zinc-finger protein essential for the switch, is regulated negatively by Notch and positively by EcR. Ttk overexpression stops endoreplication prematurely and alleviates the endocycle exit defect caused by extended Notch activity or removal of EcR function. Our results reveal a developmental pathway that includes down-regulation of Notch, activation of the EcR, up-regulation of Ttk to execute the E/A switch, and, for the first time, the genetic interaction between Notch and ecdysone signaling in regulation of cell cycle programs and differentiation.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. wumin@bio.fsu.edu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Sun
authors.forename: Laila
authors.initials: L
authors.lastname: Smith
authors.forename: Alexander
authors.initials: A
authors.lastname: Armento
authors.forename: Wu-Min
authors.initials: WM
authors.lastname: Deng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004261:DNA Replication / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism*; D005784:Gene Amplification / Q000502:physiology*; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D029721:Drosophila Proteins; C496298:E2f1 protein, Drosophila; D018398:Homeodomain Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D051880:Receptors, Notch; D011987:Receptors, Steroid; D012097:Repressor Proteins; D014157:Transcription Factors; C066381:ct protein, Drosophila; C055469:ecdysone receptor; C106513:peb protein, Drosophila; C075878:ttk protein, Drosophila; D004440:Ecdysone
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