The many faces of semaphorins: from development to pathology

Abstract

The semaphorin family is a large group of proteins controlling cell migration and axonal growth cone guidance. These proteins are bi-functional signals capable of growth promotion or growth inhibition. Initially described in the nervous system, the majority of studies related to semaphorins and semaphorin signalling are nowadays performed in model systems outside the nervous system. Here, we provide an exhaustive review of the many faces of semaphorins both during developmental, regulatory and pathological processes. Indeed, because of their crucial fundamental roles, the semaphorins and their receptors represent important targets for the development of drugs directed at a variety of diseases.

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

“…In addition, Semaphorins and their classic receptors (Plexins and Neuropilins) have been associated primarily with multiple functions, including cell migration and axon chemotaxis (for review see ref. 47). In particular, Sema3E and PlexinD1 have been reported to play an active role in vascular system development 29,48,49 , but they also control the migration of mouse thymocytes 50 and tumour cells 51 .…”

Inhibition of Semaphorin As a Novel Strategy for Therapeutic Angiogenesis

“…1,5 Semaphorins and their receptors (known as plexins) were initially characterized as signaling molecules that repel or attract axons, 6 -9 but are now recognized as critical regulators of morphogenesis and homeostasis in various organs and systems. 10,11 The semaphorin family comprises 21 genes in vertebrates and eight additional genes are found in invertebrates. These genes are divided into eight classes on the basis of the similarity of their structural domains, with classes 3 to 7 containing the vertebrate semaphorins.…”

Le facteur de survie neuronale GDNF

“…En effet, pour que la traversée de la ligne médiane s'accomplisse, il est nécessaire que, dans un premier temps, les axones commissuraux perçoivent des signaux (signaux attractifs) qui les attirent dans la plaque du plancher, [10] ; chez l'adulte, elles interviennent dans les fonctions immunitaires [11]. L'altération de leur expression ou de leurs propriétés contribue à la dissémination des cellules cancéreuses, à la vascularisation des tumeurs, ou encore à la limitation de la régéné-ration du système nerveux lésé [12]. Cette étude ouvre ainsi des perspectives thérapeutiques car l'ensemble de ce la plaque du plancher qui ressemblent à ceux qui sont induits par la perte de la signalisation Sema3B/PlexA1.…”

“…En revanche, nous avons observé, dans divers modèles de cultures neuronales, que le GDNF est capable d'inhiber l'activité de la calpaïne 1, et donc de restaurer l'expression de PlexA1 dans le cône de croissance des axones commissuraux et la réponse répulsive à Sema3B (Figure 2). De plus, nous avons observé que l'invalidation de GDNF chez la souris génère des défauts de traversée de [5,6,12]. Ces canaux appartiennent à la famille des canaux sodium sensibles à l'amiloride et des dégénérines (famille ENaC/DEG) qui comprend entre autres le canal sodium épithélial (ENaC).…”