The formation of neuromuscular synapses
- Molecular Neurobiology Program, Skirball Institute, New York University Medical Center, New York, New York 10016 USA
This extract was created in the absence of an abstract.
The formation of synapses requires a series of steps including the generation of neurons and their target cells, the guidance of axons to their targets, and the induction of a specialized presynaptic terminal and postsynaptic membrane. This review is primarily concerned with the inductive events that lead to postsynaptic differentiation. Because this phase of synapse formation begins only after motor neurons have navigated to their target muscle cells, the first section of this review summarizes our current understanding of the principles that govern the guidance of motor axons to skeletal muscle cells. The second section will review our current knowledge of signaling molecules and mechanisms that are critical for inducing postsynaptic differentiation. Although the principles and mechanisms of synapse formation are likely to be similar in the PNS and the CNS, much of our understanding about the mechanisms of synapse formation arises from studies of the vertebrate neuromuscular synapse.
Motor axons project along a stereotyped pathway from spinal cord to muscle
Much of the evidence for accurate and stereotyped pathfinding arises from studies of the developing chick embryo (Landmesser 1992). The growth cones of chick motor neurons, which are destined to innervate the limb, exit the spinal cord, extend across the rostral half of developing somites, and converge upon a plexus where they intermingle with growth cones that are destined to innervate different muscles. Recent studies suggest that T-cadherin (Fredette et al. 1996), collagen IX (Ring et al. 1996), and the Eph family ligands, HtkL/Lerk2 (Wang and Anderson 1997), which are each expressed preferentially in the caudal half of the somite, repel these motor axons from the caudal half somite and guide them across the rostral somite. Furthermore, because HtkL/Lerk2 (Wang and Anderson 1997), as well as collapsin-1 (Shepherd et al. 1996), are expressed in the dermatome, repulsive signals acting in three dimensions may guide motor axons toward the plexus.
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