title: Epidermal growth factor signalling controls myosin II planar polarity to orchestrate convergent extension movements during Drosophila tubulogenesis.
abstract: Most epithelial tubes arise as small buds and elongate by regulated morphogenetic processes including oriented cell division, cell rearrangements, and changes in cell shape. Through live analysis of Drosophila renal tubule morphogenesis we show that tissue elongation results from polarised cell intercalations around the tubule circumference, producing convergent-extension tissue movements. Using genetic techniques, we demonstrate that the vector of cell movement is regulated by localised epidermal growth factor (EGF) signalling from the distally placed tip cell lineage, which sets up a distal-to-proximal gradient of pathway activation to planar polarise cells, without the involvement for PCP gene activity. Time-lapse imaging at subcellular resolution shows that the acquisition of planar polarity leads to asymmetric pulsatile Myosin II accumulation in the basal, proximal cortex of tubule cells, resulting in repeated, transient shortening of their circumferential length. This repeated bias in the polarity of cell contraction allows cells to move relative to each other, leading to a reduction in cell number around the lumen and an increase in tubule length. Physiological analysis demonstrates that animals whose tubules fail to elongate exhibit abnormal excretory function, defective osmoregulation, and lethality.
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Aditya
authors.initials: A
authors.lastname: Saxena
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Barry
authors.initials: B
authors.lastname: Denholm
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bunt
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom; School of Biology, St Andrews, Scotland, United Kingdom.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bischoff
authors.affiliation: National Centre for Biological Sciences GKVK Campus, Bangalore, Karnataka, India.
authors.forename: Krishnaswamy
authors.initials: K
authors.lastname: VijayRaghavan
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Helen
authors.initials: H
authors.lastname: Skaer
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002465:Cell Movement; D016764:Cell Polarity; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D017344:Genes, Insect; D006706:Homeostasis; D008317:Malpighian Tubules / Q000166:cytology / Q000196:embryology*; D008954:Models, Biological; D009024:Morphogenesis; D024462:Myosin Type II / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D024462:Myosin Type II