title: Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.
abstract: The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Marc
authors.initials: M
authors.lastname: Amoyel
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Jason
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Suisse
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Johanna
authors.initials: J
authors.lastname: Glasner
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, United States of America.|The Helen L. and Martin S. Kimmel Center for Stem Cell Biology, New York University School of Medicine, New York, New York, United States of America.
authors.forename: Erika A
authors.initials: EA
authors.lastname: Bach
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000254:growth & development*; D006801:Humans; D008297:Male; D015398:Signal Transduction / Q000235:genetics; D013094:Spermatozoa / Q000166:cytology / Q000254:growth & development; D055153:Stem Cell Niche / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics*; D013737:Testis / Q000254:growth & development* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C460659:Socs36E protein, Drosophila; D050826:Suppressor of Cytokine Signaling Proteins