Getting neural circuits into shape with semaphorins View Full Text


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Article Info

DATE

2012-08-16

AUTHORS

R. Jeroen Pasterkamp

ABSTRACT

Key PointsThe semaphorins are a family of membrane-associated and secreted proteins that mediate diverse aspects of neural circuit development, ranging from neuron migration to repulsive axon guidance and synapse formation. In neurons, semaphorins signal predominantly through receptor proteins of the plexin and neuropilin families.The presentation and function of semaphorin receptors is under tight molecular control to spatiotemporally regulate the responsiveness of growth cones to semaphorins and to diversify their effects, thereby allowing semaphorins to mediate a disproportionately large number of wiring decisions.Neurons can expand their semaphorin signalling capacities by regulating the subunit composition of their receptors (thus allowing semaphorins to act as neurite attractants and repellents), and by utilizing semaphorins as ligands or receptors. Expression of semaphorin receptors is controlled at multiple different levels, including at the transcriptional and post-transcriptional levels.Although originally identified as growth cone-collapsing factors, semaphorins mediate a plethora of functions beyond axon pathfinding in the developing and mature nervous system. For example, during early development SEMA3A facilitates dendrite formation and inhibits axon specification through the activation of different cyclic GMP-dependent signalling pathways. Moreover, once neurons have been formed, secreted semaphorins (SEMA3s) and transmembrane semaphorins (SEMA5 and SEMA6) help to restrict neuronal processes to their targets in a topographical or lamina-specific manner.Upon arrival in their synaptic target fields, axons must identify their postsynaptic partners and generate synaptic contacts, often at specific cellular domains of the postsynaptic cell. Recent work in different parts of the nervous system suggests that these processes are controlled by semaphorins.Emerging evidence suggests that uncontrolled semaphorin expression and function has an important role in nervous system-related diseases and regeneration failure. Therefore, understanding the mechanistic details of semaphorin signalling and function will be crucial in the design of strategies to modulate neural injury and disease. More... »

PAGES

605-618

References to SciGraph publications

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    48 schema:description Key PointsThe semaphorins are a family of membrane-associated and secreted proteins that mediate diverse aspects of neural circuit development, ranging from neuron migration to repulsive axon guidance and synapse formation. In neurons, semaphorins signal predominantly through receptor proteins of the plexin and neuropilin families.The presentation and function of semaphorin receptors is under tight molecular control to spatiotemporally regulate the responsiveness of growth cones to semaphorins and to diversify their effects, thereby allowing semaphorins to mediate a disproportionately large number of wiring decisions.Neurons can expand their semaphorin signalling capacities by regulating the subunit composition of their receptors (thus allowing semaphorins to act as neurite attractants and repellents), and by utilizing semaphorins as ligands or receptors. Expression of semaphorin receptors is controlled at multiple different levels, including at the transcriptional and post-transcriptional levels.Although originally identified as growth cone-collapsing factors, semaphorins mediate a plethora of functions beyond axon pathfinding in the developing and mature nervous system. For example, during early development SEMA3A facilitates dendrite formation and inhibits axon specification through the activation of different cyclic GMP-dependent signalling pathways. Moreover, once neurons have been formed, secreted semaphorins (SEMA3s) and transmembrane semaphorins (SEMA5 and SEMA6) help to restrict neuronal processes to their targets in a topographical or lamina-specific manner.Upon arrival in their synaptic target fields, axons must identify their postsynaptic partners and generate synaptic contacts, often at specific cellular domains of the postsynaptic cell. Recent work in different parts of the nervous system suggests that these processes are controlled by semaphorins.Emerging evidence suggests that uncontrolled semaphorin expression and function has an important role in nervous system-related diseases and regeneration failure. Therefore, understanding the mechanistic details of semaphorin signalling and function will be crucial in the design of strategies to modulate neural injury and disease.
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