title: Heparan sulfate regulates the number and centrosome positioning of Drosophila male germline stem cells.
abstract: Stem cell division is tightly controlled via secreted signaling factors and cell adhesion molecules provided from local niche structures. Molecular mechanisms by which each niche component regulates stem cell behaviors remain to be elucidated. Here we show that heparan sulfate (HS), a class of glycosaminoglycan chains, regulates the number and asymmetric division of germline stem cells (GSCs) in the Drosophila testis. We found that GSC number is sensitive to the levels of 6-O sulfate groups on HS. Loss of 6-O sulfation also disrupted normal positioning of centrosomes, a process required for asymmetric division of GSCs. Blocking HS sulfation specifically in the niche, termed the hub, led to increased GSC numbers and mispositioning of centrosomes. The same treatment also perturbed the enrichment of Apc2, a component of the centrosome-anchoring machinery, at the hub-GSC interface. This perturbation of the centrosome-anchoring process ultimately led to an increase in the rate of spindle misorientation and symmetric GSC division. This study shows that specific HS modifications provide a novel regulatory mechanism for stem cell asymmetric division. The results also suggest that HS-mediated niche signaling acts upstream of GSC division orientation control.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Levings
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arashiro
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455 nakat003@umn.edu.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakato
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D018385:Centrosome / Q000648:ultrastructure; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology; D006497:Heparan Sulfate / Q000378:metabolism*; D008297:Male; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology; D013737:Testis / Q000378:metabolism / Q000502:physiology; D025521:Tumor Suppressor Proteins
chemical_list: D029721:Drosophila Proteins; D006497:Heparan Sulfate; D025521:Tumor Suppressor Proteins; C467323:APC2 protein, Drosophila