title: Differential Regulation of Cyclin E by Yorkie-Scalloped Signaling in Organ Development.
abstract: Tissue integrity and homeostasis are accomplished through strict spatial and temporal regulation of cell growth and proliferation during development. Various signaling pathways have emerged as major growth regulators across metazoans; yet, how differential growth within a tissue is spatiotemporally coordinated remains largely unclear. Here, we report a role of a growth modulator Yorkie (Yki), theDrosophilahomolog of Yes-associated protein (YAP), that differentially regulates its targets inDrosophilawing imaginal discs; whereby Yki interacts with its transcriptional partner, Scalloped (Sd), the homolog of the TEAD/TEF family transcription factor in mammals, to control an essential cell cycle regulator Cyclin E (CycE). Interestingly, when Yki was coexpressed with Fizzy-related (Fzr), aDrosophilaendocycle inducer and homolog of Cdh1 in mammals, surrounding hinge cells displayed larger nuclear size than distal pouch cells. The observed size difference is attributable to differential regulation of CycE, a target of Yki and Sd, the latter of which can directly bind toCycEregulatory sequences, and is expressed only in the pouch region of the wing disc starting from the late second-instar larval stage. During earlier stages of larval development, when Sd expression was not detected in the wing disc, coexpression of Fzr and Yki did not cause size differences between cells along the proximal-distal axis of the disc. We show that ectopic CycE promoted cell proliferation and apoptosis, and inhibited transcriptional activity of Yki targets. These findings suggest that spatiotemporal expression of transcription factor Sd induces differential growth regulation by Yki during wing disc development, highlighting coordination between Yki and CycE to control growth and maintain homeostasis.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4295.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Shu
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida 32306-4295 wumin@bio.fsu.edu.
authors.forename: Wu-Min
authors.initials: WM
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053145:Cell Nucleus Size / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019927:Cyclin E / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D062951:Endoreduplication / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D060227:Imaginal Discs / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D038081:Organogenesis; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: C000627647:CycE protein, Drosophila; D019927:Cyclin E; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila; C087984:sd protein, Drosophila
keywords: Yki Sd; cell growth and proliferation; differential regulation