Polycomb group genes Psc and Su(z)2 restrict follicle stem cell self-renewal and extrusion by controlling canonical and noncanonical Wnt signaling

Stem cells are critical for maintaining tissue homeostasis and are commonly governed by their niche microenvironment, although the intrinsic mechanisms controlling their multipotency are poorly understood. Polycomb group (PcG) genes are epigenetic silencers, and have emerged recently as important pl...

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Veröffentlicht in:Genes & development 2010-05, Vol.24 (9), p.933-946
Hauptverfasser: Li, Xinghua, Han, Yue, Xi, Rongwen
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Han, Yue
Xi, Rongwen
description Stem cells are critical for maintaining tissue homeostasis and are commonly governed by their niche microenvironment, although the intrinsic mechanisms controlling their multipotency are poorly understood. Polycomb group (PcG) genes are epigenetic silencers, and have emerged recently as important players in maintaining stem cell multipotency by preventing the initiation of differentiation programs. Here we describe an unexpected role of specific PcG genes in allowing adult stem cell differentiation and preventing stem cell-derived tumor development. We show that Posterior sex combs (Psc), which encodes a core Polycomb-repressive complex 1 (PRC1) component, functions redundantly with a similar gene, Suppressor of zeste two [Su(z)2], to restrict follicle stem cell (FSC) self-renewal in the Drosophila ovary. FSCs carrying deletion mutations of both genes extrude basally from the epithelium and continue to self-propagate at ectopic sites, leading to the development of FSC-like tumors. Furthermore, we show that the propagation of the mutant cells is driven by sustained activation of the canonical Wnt signaling pathway, which is essential for FSC self-renewal, whereas the epithelial extrusion is mediated through the planar cell polarity pathway. This study reveals a novel mechanism of epithelial extrusion, and indicates a novel role of polycomb function in allowing adult stem cell differentiation by antagonizing self-renewal programs. Given evolutionary conservation of PcG genes from Drosophila to mammals, they could have similar functions in mammalian stem cells and cancer.
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Polycomb group (PcG) genes are epigenetic silencers, and have emerged recently as important players in maintaining stem cell multipotency by preventing the initiation of differentiation programs. Here we describe an unexpected role of specific PcG genes in allowing adult stem cell differentiation and preventing stem cell-derived tumor development. We show that Posterior sex combs (Psc), which encodes a core Polycomb-repressive complex 1 (PRC1) component, functions redundantly with a similar gene, Suppressor of zeste two [Su(z)2], to restrict follicle stem cell (FSC) self-renewal in the Drosophila ovary. FSCs carrying deletion mutations of both genes extrude basally from the epithelium and continue to self-propagate at ectopic sites, leading to the development of FSC-like tumors. Furthermore, we show that the propagation of the mutant cells is driven by sustained activation of the canonical Wnt signaling pathway, which is essential for FSC self-renewal, whereas the epithelial extrusion is mediated through the planar cell polarity pathway. This study reveals a novel mechanism of epithelial extrusion, and indicates a novel role of polycomb function in allowing adult stem cell differentiation by antagonizing self-renewal programs. 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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Animals
Cell Differentiation
Cell Line
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Drosophila melanogaster - cytology
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila melanogaster - physiology
Drosophila Proteins - genetics
Drosophila Proteins - metabolism
Female
Gene Deletion
Glycoproteins - metabolism
Ovary - cytology
Ovary - pathology
Polycomb Repressive Complex 1
Research Paper
Signal Transduction
Stem Cells - cytology
Stem Cells - pathology
Wnt Proteins - metabolism
title Polycomb group genes Psc and Su(z)2 restrict follicle stem cell self-renewal and extrusion by controlling canonical and noncanonical Wnt signaling
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