La morphogenèse du système nerveux chez les vertébrés

Abstract

Durant la gastrulation, la différenciation neurale débute dans la partie dorsale de l’ectoderme sous l’action de signaux inhibiteurs tels que noggin, chordin, follistatin, Xnr3 et cerberus. Ces signaux, qui proviennent du centre organisateur de Spemann, permettent l’engagement d’une partie de l’ectoderme dans la voie de différenciation neurale en inhibant les facteurs de croissance de type BMP/GDF. L’engagement dans la voie neurale est accompagné d’une différenciation plus spécifique selon les trois axes de l’embryon : (1) dans l’axe dorso-ventral, celle des cellules ventrales du tube neural intervient par l’intermédiaire d’une cascade moléculaire amorcée par SHH et de facteurs de transcription tel que HNF3β; celle des cellules dorsales semble être sous le contrôle de signaux du type BMP et Wnt, et de facteurs de transcription tel que Msx et Pax ; (2) la différenciation dans l’axe antéro-postérieur semble être sous l’influence de plusieurs signaux, FGF, Wnt et l’acide rétinoïque, et de facteurs de transcription de la famille Hox, qui divise le tube neural en différents territoires moléculaires ; (3) le facteur lefty, enfin, est responsable des différences droite-gauche du tube neural.

Molecular approaches used in the studies of embryonic neural development in the vertebrate embryos have started to unravel pathways involved in neural induction and patterning of the central nervous system. Neural induction begins with signaling on the dorsal ectoderm. Factors such as noggin, chordin, follistatin and cerebrus derived from the organizer mediate this inhibition and thus unveil neural fate in the dorsal side. Downstream of this inhibition, the activity of transcription factors such as SoxD and neurogenin have been implicated with the differentiation of mature neurons. Concomitant and following morphogenetic movements of the neural plate, differentiation of subtypes of neurons begins along the three axes of the neural tube. Antero-posterior differentiation is mediated by secreted factors such as FGF and Wnts as well as retinoic acid. The Hox code also subdivides the neural tube in different A-P gene expression domains and has been suggested to mediate cell identity. Ventral differentiation seems to be mediated by signaling cascades initiated by SHH originally from the notochord and later from the floor plate. HNF3beta, a transcription factor also seems to be involved in ventral differentiation. On the dorsal side both BMPs and Wnts signaling cascades have been implicated in the establishment of dorsal neural fates. Transcription factors such as Pax3 and 7 are also involved in this differentiation which ultimately will produce the roof plate, sensory neurons and dorsal interneurons. Right left assymetry seems to be mediated by lefty (also a member of the TGFbeta family), and the transcription factor ptx2. All these influences will ultimately allow the establishment of different fates in the embryonic nervous system. [References: 61]