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Role of Semaphorins during Axon Growth and Guidance

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Axon Growth and Guidance

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 621))

Abstract

During development, neuronal growth cones navigate over long distances to reach their target and establish appropriate connections. This process is usually described as a step-by-step mechanism of growth recruiting several guidance cues with attractive and repulsive properties. Among these signals, the semaphorins define a large family of more than 20 members divided into eight classes according to their phylogenic relationship and the existence of differential structural domains or sequence motifs 1 Fig. 1). Classes I and II are found in invertebrates and classes III, IV and VII in vertebrates while class V contains members from both vertebrates and invertebrates. The class VIII corresponds to viral semaphorins. Semaphorins can be soluble proteins (classes II and III), transmembrane proteins (classes I, IV, V and VI) or membrane-bound through a glycosylphosphatidylinositol anchor (class VII). Together with plexins and scatter factor receptors, semaphorins belong to the semaphorin superfamily whose defining feature is the existence of a conserved domain: the semaphorin domain. This domain of more than 500 amino acids located at the mature protein N-terminus was first identified by Kolodkin and collaborators in 1993 2. All semaphorins also contain N-glycosylation sites and their C-terminal part is differing from one class to another. Indeed, class V contains seven copies of thrombospondin repeats, classes II–V and VII contain an immunoglobulin-like domain while class III has an N-terminus basic motif. Semaphorins are widely expressed in the developing nervous system. Initially described as guidance cues ensuring axon targeting, further studies showed that they are also key regulators of cell migration, cell death or synapse formation during nervous system development. Like other guidance cues, semaphorins are also clearly implicated in various aspects of organogenesis 3 (including lung and kidney formation or angiogenesis) and during tumor progression 4. Here, we review the major functions of semaphorins in the nervous system together with the signaling mechanisms involved both at the level of receptor complex formation and recruitment of selective intracellular pathways.

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Authors and Affiliations

  1. INSERM U575, Physiopathologie du Système Nerveux, 5 rue Blaise Pascal, 67084, Strasbourg, France

    Eric Koncina, Lise Roth & Bertand Gonthier

  2. Laboratoire de Neurobiologie du Developpement et de la Regeneration (LNDR), Centre de Neurochimie de CNRS, Strasbourg, France

    Dominique Bagnard

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  1. Eric Koncina
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  2. Lise Roth
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  4. Dominique Bagnard
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  1. Laboratoire de Neurobiologie du Developpement et de la Regeneration (LNDR), Centre de Neurochimie de CNRS, Strasbourg, France

    Dominique Bagnard Ph.D.

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Koncina, E., Roth, L., Gonthier, B., Bagnard, D. (2007). Role of Semaphorins during Axon Growth and Guidance. In: Bagnard, D. (eds) Axon Growth and Guidance. Advances in Experimental Medicine and Biology, vol 621. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76715-4_4

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