title: Following the 'tracks': Tramtrack69 regulates epithelial tube expansion in the Drosophila ovary through Paxillin, Dynamin, and the homeobox protein Mirror.
abstract: Epithelial tubes are the infrastructure for organs and tissues, and tube morphogenesis requires precise orchestration of cell signaling, shape, migration, and adhesion. Follicle cells in the Drosophila ovary form a pair of epithelial tubes whose lumens act as molds for the eggshell respiratory filaments, or dorsal appendages (DAs). DA formation is a robust and accessible model for studying the patterning, formation, and expansion of epithelial tubes. Tramtrack69 (TTK69), a transcription factor that exhibits a variable embryonic DNA-binding preference, controls DA lumen volume and shape by promoting tube expansion; the tramtrack mutation twin peaks (ttk(twk)) reduces TTK69 levels late in oogenesis, inhibiting this expansion. Microarray analysis of wild-type and ttk(twk) ovaries, followed by in situ hybridization and RNAi of candidate genes, identified the Phospholipase B-like protein Lamina ancestor (LAMA), the scaffold protein Paxillin, the endocytotic regulator Shibire (Dynamin), and the homeodomain transcription factor Mirror, as TTK69 effectors of DA-tube expansion. These genes displayed enriched expression in DA-tube cells, except lama, which was expressed in all follicle cells. All four genes showed reduced expression in ttk(twk) mutants and exhibited RNAi phenotypes that were enhanced in a ttk(twk)/+ background, indicating ttk(twk) genetic interactions. Although previous studies show that Mirror patterns the follicular epithelium prior to DA tubulogenesis, we show that Mirror has an independent, novel role in tube expansion, involving positive regulation of Paxillin. Thus, characterization of ttk(twk)-differentially expressed genes expands the network of TTK69 effectors, identifies novel epithelial tube-expansion regulators, and significantly advances our understanding of this vital developmental process.
authors.affiliation: University of Washington, Molecular and Cellular Biology Program and Department of Genome Sciences, Box 355065, Seattle, WA 98195-5065, USA.
authors.forename: Nathaniel C
authors.initials: NC
authors.lastname: Peters
authors.forename: Nathaniel H
authors.initials: NH
authors.lastname: Thayer
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kerr
authors.forename: Martin
authors.initials: M
authors.lastname: Tompa
authors.forename: Celeste A
authors.initials: CA
authors.lastname: Berg
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010053:Ovary / Q000196:embryology / Q000378:metabolism*; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C496059:Pax protein, Drosophila; D051419:Paxillin; D012097:Repressor Proteins; D014157:Transcription Factors; C103922:lama protein, Drosophila; C105790:mirr protein, Drosophila; C075878:ttk protein, Drosophila; D034281:Dynamins; C439628:shi protein, Drosophila
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