Chimio-attraction ou chimio-répulsion axonale : rôle des nétrines et des sémaphorines.

Abstract

A la fin de leur phase proliférative, les neurones postmitotiques migrent le long des axes gliaux, répondant à des indices positionnels qui permettent la localisation précise de leur corps cellulaire (ou soma). Après cette phase de migration, leurs axones établissent des connexions spécifiques avec les territoires cibles grâce à une structure terminale, le cône de croissance. Véritable tête chercheuse de la cellule, cette structure assure la navigation précise de l’axone au sein des tissus ; l’activité du cône de croissance est réglée par les conditions locales : matrice extracellulaire, molécules d’adhérence, facteurs de croissance extracellulaires diffusibles, ou champs électriques. De nouvelles protéines impliquées dans le guidage à distance des cônes de croissance ont été isolées et certains de leurs récepteurs récemment mis à jour. Il s’agit des molécules de la famille des nétrines et des sémaphorines.

In the developing nervous system, migrating cells and axons are guided to their targets by cues present in the cellular environment. At the end of last century, Cajal proposed the neurotropic hypothesis as a mechanism of axonal pathfinding during development but some of the molecules implicated in axonal guidance and their receptors have been only recently characterized. Two families of chemotropic molecules implicated in axonal pathfinding, neuronal migration and neuro-muscular connections will be considered: netrins and semaphorins. Netrins, the first characterized, are responsible of the chemoattractive activity of the floor-plate for circumferentially growing axons. They define a family of guidance cues that can function as diffusible attractants but also as diffusible repellents for different classes of cells and axons. There is a remarkable phylogenetic conservation in function of netrin proteins in guiding axons from the nervous system of nematodes and flies to higher vertebrates, and a similarly conserved role for components of the netrin receptor: the DCC subfamily defines one of these receptors involved in attractive properties during axonal guidance. Recent identification of vertebrate homologues of UNC-5 and the evidence that they are netrin-binding proteins, raises the possibility that the signalling mechanisms through which netrins elicit repulsive responses are also conserved, either for axonal pathfinding or for neuronal migrations. Finally, semaphorins define a family of chemorepulsive molecules which receptors remain to be characterized. Sema 1 is involved in collapsing of growth cones of sensory neurons and SemaIII/D affects specific subpopulations of dorsal root ganglia. Gathering together all these results, it is possible to conclude that axonal pathfinding is a complex process in which chemoattraction and chemorepulsion, mediated by phylogenetically conserved ligand-receptor systems, act simultaneously in a coordinated manner. [References: 42]