Role of Axon Guidance Molecules

Leader

Research center

17 rue Moreau
75012 Paris
José-Alain Sahel

Institution

Inserm
Université Pierre et Marie Curie
CNRS
ED158
Université Pierre et Marie Curie

Laboratory

UMRS 968
Labex Lifesenses

Mots clefs

Development
regeneration
Visual system
Évolution
axon
connections
migration
 

publications

Cariboni, A., Andrews, W. D., Memi, F., Ypsilanti, A. R., Zelina, P., Chedotal, A. and Parnavelas, J. G. (2012) 'Slit2 and Robo3 modulate the migration of GnRH-secreting neurons', Development 139: 3326-31.

Matsuoka, R. L., Jiang, Z., Samuels, I. S., Nguyen-Ba-Charvet, K. T., Sun, L. O., Peachey, N. S., Chedotal, A., Yau, K. W. and Kolodkin, A. L. (2012) 'Guidance-cue control of horizontal cell morphology, lamination, and synapse formation in the mammalian outer retina', The Journal of neuroscience : the official journal of the Society for Neuroscience 32: 6859-68.

Saha, B., Ypsilanti, A. R., Boutin, C., Cremer, H. and Chedotal, A. (2012) 'Plexin-B2 regulates the proliferation and migration of neuroblasts in the postnatal and adult subventricular zone', The Journal of neuroscience : the official journal of the Society for Neuroscience 32: 16892-905.

Mommersteeg, M. T., Andrews, W. D., Ypsilanti, A. R., Zelina, P., Yeh, M. L., Norden, J., Kispert, A., Chedotal, A., Christoffels, V. M. and Parnavelas, J. G. (2013) 'Slit-roundabout signaling regulates the development of the cardiac systemic venous return and pericardium', Circulation research 112: 465-75.

Badura, A., Schonewille, M., Voges, K., Galliano, E., Renier, N., Gao, Z., Witter, L., Hoebeek, F. E., Chedotal, A. and De Zeeuw, C. I. (2013) 'Climbing fiber input shapes reciprocity of Purkinje cell firing', Neuron 78: 700-13.

Michalski, N., Babai, N., Renier, N., Perkel, D. J., Chedotal, A. and Schneggenburger, R. (2013) 'Robo3-driven axon midline crossing conditions functional maturation of a large commissural synapse', Neuron 78: 855-68.

Zelina P, Blockus H, Zagar Y, Péres A, Friocourt F, Wu Z, Rama N, Fouquet C, Hohenester E, Tessier-Lavigne M, Schweitzer J, Roest Crollius H, Chédotal A. Signaling Switch of the Axon Guidance Receptor Robo3 during Vertebrate Evolution. Neuron. 2014 Dec 17;84(6):1258-72. doi: 10.1016/j.neuron.2014.11.004. Epub 2014 Nov 26.

Fields of research

Neurogenetics / neurodevelopment

Research Theme

Nervous systems are composed of a network of synaptic connections among excitable cells. This network develops as axons extend from presynaptic neurons and grow often long distances to reach their correct postsynaptic partners. Neuronal migration and myelination are also key processes for the formation and stabilisation of neuronal connections. For years, neurobiologists have tried to uncover the mechanisms controling axon guidance. It was found that these are highly conserved between neurons and during evolution. It was also shown that axonal connections are plastic and can be modified during normal physiological processes and in pathological conditions.

 There is mounting evidence suggesting that axon guidance errors occuring during development, are responsible for neurological deficits in particular in the visual system. One example comes from a recentwork that has shown that human patients suffering of a rare syndrome named HGPPS (horizontal gaze palsy with progressive scoliosis) have an atrophied abducens nucleus (VI), are unable to move their eyes laterally and develop a strong scoliosis. All HGPPS patients bear mutations in the ROBO3 gene. One of our goal is is to understand the function of Robo3 in the oculomotor system.

 The discovery of neural stem cells in the adult brain was a major finding of the recent years. In many models of lesion of the nervous system, neural stem cells can be derived from their usual migration pathway to integrate the injured region. We are characterizing new molecules controlling neural stem cell development and physiology and determine their ability to promote the regenerative potential of neural on stem cells. These studies could lead to the development of new therapeutic tools to stimulate stem cell migration and differentiation in the visual system.

Etudiants ENP

Heike BLOCKUS

Lab rotation

A new method to analyze at unprecedented resolution the development of the Human Nervous System.

Chercheur responsable: 

CHEDOTAL Alain

Dates: 

18 September 2017 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Sept-Dec 2017 (to be discussed)

~ Jan-March 2018

~ April-June 2018

Project

Combining whole-mount immunocytochemistry with tissue-clearing and light-sheet microscopy 3D analysis of embryonic and fetal specimens, we now seek to decipher the mechanisms ruling the organization of the human nervous system and associated tissues; to reconstitute the embryonic landscape of axon guidance cues, and to enhance our understanding of neuronal fate allocation and brain patterning. This project is a decisive progress towards grasping the etiology of congenital neuropathies.

Reference:  Belle, M., Godefroy D., Couly G., Malone, S.A., Collier F., Giacobini, P. and Chédotal A. (2017) Tridimensional visualization and analysis of early human development. Cell,169:161-173

Contact

Institut de la Vision - 17, rue Moreau 75012 Paris - +33 1 53 46 25 15 - alain.chedotal@inserm.fr

Superviseur: 

CHEDOTAL Alain