Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals.
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.
Fox
Michael A
MA
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Sanes
Joshua R
JR
Borza
Dorin-Bogdan
DB
Eswarakumar
Veraragavan P
VP
Fässler
Reinhard
R
Hudson
Billy G
BG
John
Simon W M
SW
Ninomiya
Yoshifumi
Y
Pedchenko
Vadim
V
Pfaff
Samuel L
SL
Rheault
Michelle N
MN
Sado
Yoshikazu
Y
Segal
Yoav
Y
Werle
Michael J
MJ
Umemori
Hisashi
H
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
D001324:Autoantigens; D024141:Collagen Type IV; D007797:Laminin; D011994:Recombinant Proteins; C057112:type IV collagen alpha3 chain; C058783:laminin beta2; D005346:Fibroblast Growth Factors