title: Mesenchymal-to-epithelial transition of intercalating cells in Drosophila renal tubules depends on polarity cues from epithelial neighbours.
abstract: The intercalation of mesenchymal cells into epithelia, through mesenchymal-to-epithelial transition (MET), underlies organogenesis, for example, in nephrogenesis, and tissue regeneration, during cell renewal and wound repair. Despite its importance, surprisingly little is known about the mechanisms that bring about MET in comparison with the related and much-studied, reverse process, epithelial-to-mesenchymal transition (EMT). We analyse the molecular events that regulate MET as stellate cells integrate into the established epithelium of the developing renal tubules in Drosophila. We show that stellate cells polarise as they integrate between epithelial principal cells and that the normal, localised expression of cell polarity proteins in principal cells is required for stellate cells to become epithelial. While the basolateral and apical membranes act as cues for stellate cell polarity, adherens junction integrity is required to regulate their movement through the epithelium; in the absence of these junctions stellate cells continue migrating into the tubule lumen. We also show that expression of basolateral proteins in stellate cells is a prerequisite for their ingression between principal cells. We present a model in which the contacts with successive principal cell membrane domains made by stellate cells as they integrate between them act as a cue for the elaboration of stellate cell polarity. We suggest that the formation of zonula adherens junctions between new cell neighbours establishes their apico-basal positions and stabilises them in the epithelium.
authors.affiliation: Institut de Biologia Molecular de Barcelona-CSIC, Parc Cientific de Barcelona, 08028 Barcelona, Spain.
authors.forename: Kyra
authors.initials: K
authors.lastname: Campbell
authors.forename: Jordi
authors.initials: J
authors.lastname: Casanova
authors.forename: Helen
authors.initials: H
authors.lastname: Skaer
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D004848:Epithelium / Q000196:embryology* / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology* / Q000196:embryology; D008648:Mesoderm / Q000166:cytology* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins
references.citation: Genes Dev. 1996 Mar 15;10(6):672-85
references.pmid: 8598295
references.citation: Development. 2005 Mar;132(5):1105-16
references.pmid: 15689372
references.citation: Genes Dev. 1996 Mar 15;10(6):659-71
references.pmid: 8598294
references.citation: Am J Pathol. 2002 Jun;160(6):2181-90
references.pmid: 12057921
references.citation: Development. 2002 Feb;129(4):935-44
references.pmid: 11861476
references.citation: Dev Biol. 1994 Feb;161(2):563-96
references.pmid: 8314002
references.citation: Oncogene. 2008 Nov 24;27(55):6958-69
references.pmid: 19029937
references.citation: Dev Cell. 2008 Nov;15(5):704-13
references.pmid: 19000835
references.citation: Nature. 2004 Jun 10;429(6992):667-71
references.pmid: 15190355
references.citation: Dev Cell. 2004 Mar;6(3):343-55
references.pmid: 15030758
references.citation: Exp Cell Res. 2005 Jan 15;302(2):206-20
references.pmid: 15561102
references.citation: Nat Neurosci. 2002 Apr;5(4):316-24
references.pmid: 11914720
references.citation: J Exp Biol. 1996 May;199(Pt 5):1163-75
references.pmid: 8786336
references.citation: J Cell Sci. 2009 Aug 1;122(Pt 15):2604-12
references.pmid: 19567473
references.citation: Nature. 2003 Mar 20;422(6929):326-30
references.pmid: 12629552
references.citation: J Cell Biol. 2005 Aug 29;170(5):803-12
references.pmid: 16129787
references.citation: Dev Biol. 1995 Jun;169(2):609-18
references.pmid: 7781902
references.citation: Cell. 1995 Jul 14;82(1):67-76
references.pmid: 7606787
references.citation: Curr Biol. 2003 Jun 17;13(12):1052-7
references.pmid: 12814552
references.citation: Dev Biol. 1998 Nov 15;203(2):435-50
references.pmid: 9808792
references.citation: Development. 2005 May;132(10):2389-400
references.pmid: 15843408
references.citation: Development. 1994 Mar;120(3):579-90
references.pmid: 8162857
references.citation: Bioessays. 1997 Aug;19(8):673-82
references.pmid: 9264249
references.citation: Development. 2006 Jul;133(13):2507-15
references.pmid: 16728476