Group leader, Research Director (DR1), Coordinator of the Development Department
Vision Institute, Paris, France Inserm, France
Alain Chédotal is interested in deciphering how, on one hand migrating neurons and on the other hand neuron extensions are guided in the developing brain in order to establish connections between one another (axons). He is also working with his team on new technologies allowing the visualization of developing neurons. Their research should determine whether molecules involved in axonal guidance are also players of diseases of the visual system or demyelinating pathologies like multiple sclerosis or certain cancers.
Nervous systems are composed of a network of synaptic connections among excitable cells, neurons. 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 stabilization 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.
The goal of Alain Chedotal’s research is to understand how growing axons and migrating neurons are guided in the brain, since their origin to their target. He is also working on new technologies allowing the visualization of developing neurons and trying to understand the myelination process.
More precisely, Alain Chédotal and his team are working along four lines of research :
1/ analysis of the role of guidance molecules in neuronal connections : they particularly study axon growth at the central nervous system midline (notably the optic chiasma in the visual system)
2/ utilization of new microscopy analysis methods to study the organizations of neuronal connections in sensorial nervous systems (visual and auditory)
3/ study of the function of axonal guidance molecules (in particular slits and semaphorins) in the control of neuronal migration control during development and in the adult brain. They are trying to determine whether those molecules control neural stem cell migration in normal and/or pathological conditions
4/ study of the role of axonal guidance molecules in the process of myelination. They are developing new methods in video-microscopy to study myelination.
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. Alain Chedotal and his team 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.
• 1988 : Admitted to the Ecole Normale Supérieure, Lyon, France
• 1995 : Ph. D. in Neurosciences, University Paris 6 UPMC, France, Constantino Sotelo’s lab
• 1995-1997 : Post-doctoral fellow (EMBO long term fellow), UC Berkeley, USA, Corey S Goodman’s lab
• Remedios Caro Almela Prize in Developmental Neurobiology, 2017
• Team Foundation for the Medical Research (FRM), 2012
• European Society of Neurochemistry, Young Investigator, 2001
• Team Foundation for the Medical Research (FRM), 2006
Creation of the first database of 3D embryo Imaging.
Many articles in the general press following publication in Cell :
Sciences et avenir
Pour la science
Des neurones de toutes les couleurs
Genetic dissection of the function of hindbrain axonal commissures
March 2010, PLoS Biology
Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in migrating granule cells
Apr 2008, Nat Neuroscience
The transmembrane semaphorin Sema6A controls cerebellar granule cell migration
Nov 2005, Nat Neuroscience