Distinct Target-Derived Signals Organize Formation, Maturation, and Maintenance of Motor Nerve Terminals

Michael A. Fox, Joshua R. Sanes, Dorin Bogdan Borza, Veraragavan P. Eswarakumar, Reinhard Fässler, Billy G. Hudson, Simon W.M. John, Yoshifumi Ninomiya, Vadim Pedchenko, Samuel L. Pfaff, Michelle N Rheault, Yoshikazu Sado, Yoav Segal, Michael J. Werle, Hisashi Umemori

Research output: Contribution to journalArticlepeer-review

208 Scopus citations


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, β2 laminins, and collagen α(IV) chains. FGFs of the 7/10/22 subfamily and broadly distributed collagen IV chains (α1/2) promote clustering of synaptic vesicles as nerve terminals form. β2 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 (α3-6) 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.

Original languageEnglish (US)
Pages (from-to)179-193
Number of pages15
Issue number1
StatePublished - Apr 6 2007

Bibliographical note

Funding Information:
We thank Dr. W.S. Lane for protein microsequencing and Dr. H. Ogawa, Dr. T. Tonezawa, and S. Kren for assistance. This work was supported by grants from NIH/NINDS to J.R.S., from NIH/NIAMS to V.P.E., to NIH/NIDDK to B.G.H., and from JSPS to Y.N.




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