Guidage axonal

Le guidage axonal est une branche du neurodéveloppement. Elle étudie comment les axones parviennent à trouver leurs cellules cibles notamment grâce aux cônes de croissance. Le principe élémentaire du guidage axonal repose sur la chemoattraction et la chemorepulsion :

Le cône de croissance est attiré par des molécules présentes dans le milieu extracellulaire et sécrétées par les cellules de sa zone de destination (ex: des facteurs de croissance).
La croissance du cône est, au contraire, inhibée par d'autres molécules émises par les zones entourant son corps cellulaire, son trajet axonal et sa zone d'arrivée. L'axone est ainsi "contraint" de suivre un guide qui lui assure de trouver sa cible sans se perdre dans une autre structure en chemin. Pour chaque trajet d'axone il y a donc une combinaison de facteurs attractifs et répulsifs que l'axone doit reconnaitre en exprimant à la surface de son cône de croissance les récepteurs adéquats.

De plus, les axones se regroupent par affin

Elucidating the role of Hmx1 during mouse development

Linda Bapst

This thesis focuses on the study of H6 homeobox 1 (HMX1) gene, a homeobox-containing transcription factor involved in sensory organ and eye development and responsible for the oculo-auricular syndrome of Schorderet-Munier-Franceschetti. The purpose of my study is to better understand the mechanism and role of this transcription factor. My thesis is divided into three parts. The first part proposes a predictive promoter model approach to identify new HMX1 target gene. The second part concerns an animal model of Hmx1 mutation, the dumbo mouse model, and brings a new insight into lethal craniofacial defects. The third part concerns the characterization of the visual capacity of the dumbo mice and a description of a new pattern of vision-linked defects. In the first part we propose a predictive promoter model approach based on transcriptomic analysis of post-natal day 15 mouse retina from dumbo and wild type mouse. This method revealed that Sgcg, Tshz2 and Slc6a9 were Hmx1 targets in the mouse retina. Ptpro, Sema3f, and Epha6 belong to the retinal axon guidance pathway and play an important role in retinotopic mapping. Significant enrichment of HMX1 binding site confirmed this pathway and we validated the transcriptional activity of Hmx1 on Ptpro, Sema3f and Sgcg by Luciferase assay. In the second part of the project we investigate the dumbo mouse model, carrying a stop codon in Hmx1, and representing the first animal model for the oculo-auricular syndrome of Schorderet-Munier-Franceschetti. The homozygous Hmx1dmbo is a semi-lethal mutation and stillborns present severe craniofacial defects, including cleft palate, chest defect and bone hypoplasia of maxilla, zygomatic process, mandible and frontal. In the third part of the thesis we provide a complete description of the vision in dumbo mouse. Despite a normal retinal phenotype, the vision of this mouse is completely impaired. We demonstrate that this was caused by abnormal retinotopic mapping and optic nerve hypoplasia. In dumbo mice the retinal ganglion cells axon projections failed to target the visual output, namely the dorsal lateral geniculate nucleus and the superior colliculus, and present abnormal patterning.

EPFL2015

Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins

Greta Limoni

The establishment of neuronal circuits requires neurons to develop and maintain appropriate connections with cellular partners in and out the central nervous system. These phenomena include elaboration of dendritic arborization and formation of synaptic contacts, initially made in excess. Subsequently, refinement occurs, and pruning takes places both at axonal and synaptic level, defining a homeostatic balance maintained throughout the lifespan. All these events require genetic regulations which happens cell-autonomously and are strongly influenced by environmental factors. This review aims to discuss the involvement of guidance cues from the Semaphorin family.

MDPI2021

Elucidating the role of Hmx1 during mouse development

Linda Bapst

EPFL2015

A Microfluidic Device to Study Axon Growth and Guidance

Elucidating the role of Hmx1 during mouse development

Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins

A Microfluidic Device to Study Axon Growth and Guidance

Elucidating the role of Hmx1 during mouse development

Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins