Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals

Cell. 2007 Apr 6;129(1):179-93. doi: 10.1016/j.cell.2007.02.035.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoantigens / metabolism
  • Cells, Cultured
  • Chick Embryo
  • Coculture Techniques
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism*
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Laminin / genetics
  • Laminin / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / cytology*
  • Motor Neurons / metabolism
  • Myoblasts / cytology
  • Myoblasts / metabolism
  • Neuromuscular Junction / embryology*
  • Neuromuscular Junction / metabolism*
  • Presynaptic Terminals / metabolism
  • Recombinant Proteins / metabolism


  • Autoantigens
  • Collagen Type IV
  • Laminin
  • Recombinant Proteins
  • type IV collagen alpha3 chain
  • laminin beta2
  • Fibroblast Growth Factors