Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis
Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline ste...
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| creator | Stine, Rachel R Greenspan, Leah J Ramachandran, Kapil V Matunis, Erika L |
| description | Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche. |
| doi_str_mv | 10.1371/journal.pgen.1004713 |
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Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1004713</identifier><identifier>PMID: 25375180</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Biology and Life Sciences ; Cell adhesion & migration ; Cell Differentiation - genetics ; Cloning ; Competition ; Cysts ; Drosophila ; Drosophila melanogaster ; Gene Expression Regulation, Developmental ; Genetic aspects ; Genetic regulation ; Genetic research ; Germ Cells - growth & development ; Germ Cells - metabolism ; Humans ; Insects ; Janus Kinases - biosynthesis ; Janus Kinases - genetics ; Kinases ; Ligands ; Male ; Nerve Tissue Proteins - biosynthesis ; Nerve Tissue Proteins - genetics ; Proteins ; Receptors, Immunologic - biosynthesis ; Receptors, Immunologic - genetics ; Roundabout Proteins ; Signal Transduction ; STAT Transcription Factors - biosynthesis ; STAT Transcription Factors - genetics ; Stem Cell Niche - genetics ; Stem cell research ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Testis - growth & development ; Testis - metabolism</subject><ispartof>PLoS genetics, 2014-11, Vol.10 (11), p.e1004713-e1004713</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Stine et al 2014 Stine et al</rights><rights>2014 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Testis. PLoS Genet 10(11): e1004713. doi:10.1371/journal.pgen.1004713</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764t-39ce6d213afe853f497b27078bf4a347dd4827c1a3a0babfa0a44d0e18ce7f7f3</citedby><cites>FETCH-LOGICAL-c764t-39ce6d213afe853f497b27078bf4a347dd4827c1a3a0babfa0a44d0e18ce7f7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222695/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4222695/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25375180$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Buszczak, Michael</contributor><creatorcontrib>Stine, Rachel R</creatorcontrib><creatorcontrib>Greenspan, Leah J</creatorcontrib><creatorcontrib>Ramachandran, Kapil V</creatorcontrib><creatorcontrib>Matunis, Erika L</creatorcontrib><title>Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. 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Greenspan, Leah J ; Ramachandran, Kapil V ; Matunis, Erika L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c764t-39ce6d213afe853f497b27078bf4a347dd4827c1a3a0babfa0a44d0e18ce7f7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Cell adhesion & migration</topic><topic>Cell Differentiation - genetics</topic><topic>Cloning</topic><topic>Competition</topic><topic>Cysts</topic><topic>Drosophila</topic><topic>Drosophila melanogaster</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genetic aspects</topic><topic>Genetic regulation</topic><topic>Genetic research</topic><topic>Germ Cells - growth & development</topic><topic>Germ Cells - metabolism</topic><topic>Humans</topic><topic>Insects</topic><topic>Janus Kinases - biosynthesis</topic><topic>Janus Kinases - genetics</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Male</topic><topic>Nerve Tissue Proteins - biosynthesis</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Proteins</topic><topic>Receptors, Immunologic - biosynthesis</topic><topic>Receptors, Immunologic - genetics</topic><topic>Roundabout Proteins</topic><topic>Signal Transduction</topic><topic>STAT Transcription Factors - biosynthesis</topic><topic>STAT Transcription Factors - genetics</topic><topic>Stem Cell Niche - genetics</topic><topic>Stem cell research</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Testis - growth & development</topic><topic>Testis - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stine, Rachel R</creatorcontrib><creatorcontrib>Greenspan, Leah J</creatorcontrib><creatorcontrib>Ramachandran, Kapil V</creatorcontrib><creatorcontrib>Matunis, Erika L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stine, Rachel R</au><au>Greenspan, Leah J</au><au>Ramachandran, Kapil V</au><au>Matunis, Erika L</au><au>Buszczak, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2014-11-01</date><risdate>2014</risdate><volume>10</volume><issue>11</issue><spage>e1004713</spage><epage>e1004713</epage><pages>e1004713-e1004713</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25375180</pmid><doi>10.1371/journal.pgen.1004713</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biology and Life Sciences Cell adhesion & migration Cell Differentiation - genetics Cloning Competition Cysts Drosophila Drosophila melanogaster Gene Expression Regulation, Developmental Genetic aspects Genetic regulation Genetic research Germ Cells - growth & development Germ Cells - metabolism Humans Insects Janus Kinases - biosynthesis Janus Kinases - genetics Kinases Ligands Male Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Proteins Receptors, Immunologic - biosynthesis Receptors, Immunologic - genetics Roundabout Proteins Signal Transduction STAT Transcription Factors - biosynthesis STAT Transcription Factors - genetics Stem Cell Niche - genetics Stem cell research Stem cells Stem Cells - cytology Stem Cells - metabolism Testis - growth & development Testis - metabolism |
| title | Coordinate regulation of stem cell competition by Slit-Robo and JAK-STAT signaling in the Drosophila testis |
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