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 organiz...

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Bibliographic Details
Published in:Cell 2007-04, Vol.129 (1), p.179-193
Main Authors: Fox, Michael A., Sanes, Joshua R., Borza, Dorin-Bogdan, Eswarakumar, Veraragavan P., Fässler, Reinhard, Hudson, Billy G., John, Simon W.M., Ninomiya, Yoshifumi, Pedchenko, Vadim, Pfaff, Samuel L., Rheault, Michelle N., Sado, Yoshikazu, Segal, Yoav, Werle, Michael J., Umemori, Hisashi
Format: Article
Language:English
Subjects:
Animals
Autoantigens - metabolism
Cells, Cultured
Chick Embryo
Coculture Techniques
Collagen Type IV - genetics
Collagen Type IV - metabolism
DEVBIO
Fibroblast Growth Factors - metabolism
Humans
Laminin - genetics
Laminin - metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
MOLNEURO
Motor Neurons - cytology
Motor Neurons - metabolism
Myoblasts - cytology
Myoblasts - metabolism
Neuromuscular Junction - embryology
Neuromuscular Junction - metabolism
Presynaptic Terminals - metabolism
Recombinant Proteins - metabolism
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2007.02.035