title: Septin-driven coordination of actin and microtubule remodeling regulates the collateral branching of axons.
abstract: Axon branching is fundamental to the development of the peripheral and central nervous system. Branches that sprout from the axon shaft are termed collateral or interstitial branches. Collateral branching of axons requires the formation of filopodia from actin microfilaments (F-actin) and their engorgement with microtubules (MTs) that splay from the axon shaft. The mechanisms that drive and coordinate the remodeling of actin and MTs during branch morphogenesis are poorly understood. Septins comprise a family of GTP-binding proteins that oligomerize into higher-order structures, which associate with membranes and the actin and microtubule cytoskeleton. Here, we show that collateral branching of axons requires SEPT6 and SEPT7, two interacting septins. In the axons of sensory neurons, both SEPT6 and SEPT7 accumulate at incipient sites of filopodia formation. We show that SEPT6 localizes to axonal patches of F-actin and increases the recruitment of cortactin, a regulator of Arp2/3-mediated actin polymerization, triggering the emergence of filopodia. Conversely, SEPT7 promotes the entry of axonal MTs into filopodia, enabling the formation of collateral branches. Surprisingly, septins provide a novel mechanism for the collateral branching of axons by coordinating the remodeling of the actin and microtubule cytoskeleton.
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Jianli
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Bai
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Bowen
authors.forename: Lee
authors.initials: L
authors.lastname: Dolat
authors.forename: Farida
authors.initials: F
authors.lastname: Korobova
authors.forename: Wenqian
authors.initials: W
authors.lastname: Yu
authors.forename: Peter W
authors.initials: PW
authors.lastname: Baas
authors.forename: Tatyana
authors.initials: T
authors.lastname: Svitkina
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gallo
authors.forename: Elias T
authors.initials: ET
authors.lastname: Spiliotis
mesh_terms: D000199:Actins / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D015153:Blotting, Western; D002642:Chick Embryo; D051356:Cortactin / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005727:Ganglia, Spinal / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology* / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology; D007091:Image Processing, Computer-Assisted; D047468:Immunoprecipitation; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D011554:Pseudopodia / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D058112:Septins / Q000378:metabolism* / Q000502:physiology; D059008:Time-Lapse Imaging
chemical_list: D000199:Actins; D051356:Cortactin; D017931:DNA Primers; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D058112:Septins