Axon guidance

Summary

Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research. Axon growth takes place from a region called the growth cone and reaching the axon target is accomplished with relatively few guidance molecules. Growth cone receptors respond to the guidance cues. Mechanisms Growing axons have a highly motile structure at the growing tip called the growth cone, which responds to signals in the extracellular environment that instruct the axon in which direction to grow. These signals, called guidance cues, can be fixed in place or diffusible; they can attract or repel axons. Growth cones contain receptors that recognize these guidance cues and interpret the signal into a chemotropic response. The general theoretical framework is th

Official source

https://en.wikipedia.org/wiki/Axon_guidance

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A Microfluidic Device to Study Axon Growth and Guidance

Sarra de Valence

[...] Studying axon guidance by diffusible or substrate bound gradients is challenging with current techniques. In this study, we present two microfluidic devices to study axon guidance. [... click on "Download fulltext" for full abstract]

2008

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

EPFL2015