title: Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals.
abstract: Target-derived factors organize synaptogenesis by promoting differentiation of nerve terminals at synaptic sites. Several candidate organizing molecules have been identified based on their bioactivities in vitro, but little is known about their roles in vivo. Here, we show that three sets of organizers act sequentially to pattern motor nerve terminals: FGFs, beta2 laminins, and collagen alpha(IV) chains. FGFs of the 7/10/22 subfamily and broadly distributed collagen IV chains (alpha1/2) promote clustering of synaptic vesicles as nerve terminals form. beta2 laminins concentrated at synaptic sites are dispensable for embryonic development of nerve terminals but are required for their postnatal maturation. Synapse-specific collagen IV chains (alpha3-6) accumulate only after synapses are mature and are required for synaptic maintenance. Thus, multiple target-derived signals permit discrete control of the formation, maturation, and maintenance of presynaptic specializations.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fox
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.forename: Dorin-Bogdan
authors.initials: DB
authors.lastname: Borza
authors.forename: Veraragavan P
authors.initials: VP
authors.lastname: Eswarakumar
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Billy G
authors.initials: BG
authors.lastname: Hudson
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Vadim
authors.initials: V
authors.lastname: Pedchenko
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Rheault
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Yoav
authors.initials: Y
authors.lastname: Segal
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Werle
authors.forename: Hisashi
authors.initials: H
authors.lastname: Umemori
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D018920:Coculture Techniques; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D009469:Neuromuscular Junction / Q000196:embryology* / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D001324:Autoantigens; D024141:Collagen Type IV; D007797:Laminin; D011994:Recombinant Proteins; C057112:type IV collagen alpha3 chain; C058783:laminin beta2; D005346:Fibroblast Growth Factors