IMR Press / FBL / Volume 8 / Issue 6 / DOI: 10.2741/1080

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
The function of semaphorins during nervous system development
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1 Abteilung Molekularbiologie, Institut fur Allgemeine Zoologie und Genetik, Westfalische Wilhelms-Universität, Schlobplatz 5, 48149 Münster, Germany

Academic Editor: Michael Hortsch

Front. Biosci. (Landmark Ed) 2003, 8(6), 484–499; https://doi.org/10.2741/1080
Published: 1 May 2003
(This article belongs to the Special Issue Neural cell adhesion molecules)
Abstract

The wiring of the nervous system is established through a progressive refinement of the choices made by a growing axon. The growth cone is a highly motile structure at the tip of the axon that integrates the multitude of signals present in its environment and translates these signals into structural changes of the cytoskeleton that determine the rate and direction of extension. Four families of guidance cues were identified that provide directional information to growing axons: the ephrins, the netrins, the slit proteins, and the semaphorins. The semaphorins represent the largest family of guidance cues identified so far that can be divided into 8 classes based on the degree of sequence similarity between their semaphorin domains and the presence of class specific carboxy-terminal domains (CTD). Collectively, the in vitro data indicate that semaphorins function mainly as chemorepellents that direct axons away from tissues marked by their expression, but can also act as chemoattractants in some cases. Genetic analysis of the semaphorins and their receptor showed that these proteins play an important role in the development and function of different tissues other than the nervous system. The effects of the different semaphorins are mediated by a variety of receptor complexes that include members of the neuropilin and plexin protein families as well as other membrane proteins belonging to the immunoglobulin superfamily. Plexins directly and indirectly interact with members of the Rho-like GTPases, the kinases Fes, Fyn, and Cdk5, the oxidoreductase MICAL, lipoxygenase, and the CRMP proteins. The signal transduction cascades that include these signalling proteins and link semaphorin receptors to the cytoskeleton are still incompletely understood.

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