A genome-scale in vivo RNAi analysis of epithelial development in Drosophila identifies new proliferation domains outside of the stem cell niche.
The Drosophila oogenesis system provides an excellent model to study the development of epithelial tissues. Here, we report the first genome-scale in vivo RNA interference (RNAi) screen for genes controlling epithelial development. By directly analysing cell and tissue architecture we identified 1125 genes, which we assigned to seven different functions in epithelial formation and homeostasis. We validated the significance of our screen by generating mutants for Vps60, a component of the endosomal sorting complexes required for transport (ESCRT) machinery. This analysis provided new insights into spatiotemporal control of cell proliferation in the follicular epithelium. Previous studies have identified signals controlling divisions in the follicle stem cell niche. However, 99% of cell divisions occur outside of the niche and it is unclear how these divisions are controlled. Our data distinguish two new domains outside of the stem cell niche where there are differing controls on proliferation. One domain abuts the niche and is characterised by ESCRT, Notch and JAK/STAT-mediated control of proliferation. Adjacent to this domain, another domain is defined by loss of the impact of ESCRT on cell division. Thus, during development epithelial cells pass through a variety of microenvironments that exert different modes of proliferation control. The switch between these modes might reflect a decrease in the 'stemness' of epithelial cells over time.
Heidelberg University, Medical Faculty Mannheim, Department of Cell and Molecular Biology and German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, Ludolf-Krehl-Strasse 13-17, D-68167 Mannheim, Germany.
Nicola
N
Berns
Heidelberg University, Medical Faculty Mannheim, Department of Cell and Molecular Biology and German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, Ludolf-Krehl-Strasse 13-17, D-68167 Mannheim, Germany.
Innokenty
I
Woichansky
Heidelberg University, Medical Faculty Mannheim, Department of Cell and Molecular Biology and German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, Ludolf-Krehl-Strasse 13-17, D-68167 Mannheim, Germany.
Steffen
S
Friedrichsen
Heidelberg University, Medical Faculty Mannheim, Department of Cell and Molecular Biology and German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, Ludolf-Krehl-Strasse 13-17, D-68167 Mannheim, Germany.
Nadine
N
Kraft
Heidelberg University, Medical Faculty Mannheim, Department of Cell and Molecular Biology and German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, Ludolf-Krehl-Strasse 13-17, D-68167 Mannheim, Germany veit.riechmann@medma.uni-heidelberg.de.
Veit
V
Riechmann
D000818:Animals; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D055785:Gene Knockdown Techniques; D049750:Genome, Insect; D009866:Oogenesis; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D034622:RNA Interference; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D055153:Stem Cell Niche; D025801:Ubiquitin / Q000378:metabolism
D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C497759:N protein, Drosophila; D051880:Receptors, Notch; D025801:Ubiquitin
Drosophila oogenesis; ESCRT; Epithelial development; In vivo RNAi; Notch; Vps60