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 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.
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Rachel R
RR
Stine
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Leah J
LJ
Greenspan
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Kapil V
KV
Ramachandran
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Erika L
EL
Matunis
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D053612:Janus Kinases / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D050791:STAT Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000254:growth & development / Q000378:metabolism*; D000097905:Roundabout Proteins
D053612:Janus Kinases; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D050791:STAT Transcription Factors; D000097905:Roundabout Proteins