title: COP9-Hedgehog axis regulates the function of the germline stem cell progeny differentiation niche in the Drosophila ovary.
abstract: Both stem cell self-renewal and lineage differentiation are controlled extrinsically as well as intrinsically. Germline stem cells (GSCs) in the Drosophila ovary provide an attractive model in which to study both stem cell self-renewal and lineage differentiation at the molecular and cellular level. Recently, we have proposed that escort cells (ECs) form a differentiation niche to control GSC lineage specification extrinsically. However, it remains poorly understood how the maintenance and function of the differentiation niche are regulated at the molecular level. Here, this study reveals a new role of COP9 in the differentiation niche to modulate autocrine Hedgehog (Hh) signaling, thereby promoting GSC lineage differentiation. COP9, which is a highly conserved protein complex composed of eight CSN subunits, catalyzes the removal of Nedd8 protein modification from target proteins. Our genetic results have demonstrated that all the COP9 components and the hh pathway components, including hh itself, are required in ECs to promote GSC progeny differentiation. Interestingly, COP9 is required in ECs to maintain Hh signaling activity, and activating Hh signaling in ECs can partially bypass the requirement for COP9 in GSC progeny differentiation. Finally, both COP9 and Hh signaling in ECs promote GSC progeny differentiation partly by preventing BMP signaling and maintaining cellular processes. Therefore, this study has demonstrated that the COP9-Hh signaling axis operates in the differentiation niche to promote GSC progeny differentiation partly by maintaining EC cellular processes and preventing BMP signaling. This provides new insight into how the function of the differentiation niche is regulated at the molecular level.
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Tinglin
authors.initials: T
authors.lastname: Lu
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS 66160, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Song
authors.affiliation: Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China nijq@mail.tsinghua.edu.cn tgx@stowers.org.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Ni
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS 66160, USA nijq@mail.tsinghua.edu.cn tgx@stowers.org.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D002454:Cell Differentiation; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D046912:Multiprotein Complexes / Q000378:metabolism*; D010053:Ovary / Q000166:cytology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology*
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C064196:dpp protein, Drosophila; C077245:hh protein, Drosophila; D010447:Peptide Hydrolases; C501491:CSN5 protein, Drosophila; D000075686:COP9 Signalosome Complex
keywords: COP9; Differentiation; Hh; Niche; Stem cells