title: ErbB signaling has a role in radial sorting independent of Schwann cell number.
abstract: In the peripheral nervous system, Schwann cells make myelin, a specialized sheath that is essential for rapid axonal conduction of action potentials. Immature Schwann cells initially interact with many axons, but, through a process termed radial sorting, eventually interact with one segment of a single axon as promyelinating Schwann cells. Previous studies have identified genes that are required for Schwann cell process extension and proliferation during radial sorting. Previous analyses also show that ErbB signaling is required for Schwann cell proliferation, myelination, radial sorting, and the proper formation of unmyelinated Remak bundles. Because ErbB signaling and Schwann cell proliferation are both required during radial sorting, we sought to determine if the primary function of ErbB signaling in this process is to regulate Schwann cell proliferation or if ErbB signaling also controls other aspects of radial sorting. To address this question, we applied small molecule inhibitors in vivo in zebrafish to independently block ErbB signaling and proliferation. Ultrastructural analysis of treated animals revealed that both ErbB signaling and Schwann cell proliferation are required for radial sorting in vivo. ErbB signaling, however, is required for Schwann cell process extension, while Schwann cell proliferation is not. These results provide in vivo evidence that ErbB signaling plays a direct role in process extension during radial sorting, in addition to its role in regulating Schwann cell proliferation.
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, California, USA.
authors.forename: Alya R
authors.initials: AR
authors.lastname: Raphael
authors.forename: David A
authors.initials: DA
authors.lastname: Lyons
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
mesh_terms: D000165:Acridine Orange; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D053403:Lateral Line System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D018739:Oncogene Proteins v-erbB / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D014404:Tubulin / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
chemical_list: D051767:Early Growth Response Protein 2; D004791:Enzyme Inhibitors; D051858:Forkhead Transcription Factors; D004676:Myelin Basic Protein; D018739:Oncogene Proteins v-erbB; D027701:Organic Cation Transport Proteins; D014404:Tubulin; D029961:Zebrafish Proteins; C491002:foxd3 protein, zebrafish; D049452:Green Fluorescent Proteins; D000165:Acridine Orange