Codes of intracellular signals for axon guidance

Leader

Research center

17 rue Moreau
75012 Paris
José-Alain Sahel

Institution

CNRS
Université Pierre et Marie Curie
Inserm
ED3C
UPMC

Laboratory

Phone: (+33) 1 53 46 25 57
UMRS968 UMR7210 UM80
Labex Lifesenses
Available to host a PhD student

publications

Averaimo S*, Assali A*, Couvet S, Zagar Y, Ioana Genescu I, Rebsam A, Nicol X. Local cAMP signaling restricted to lipid rafts isrequired for the developmental refinement of axonal arbors. In preparation. Under review, Nature Communications

Averaimo S, Nicol X. Intermingled cAMP, cGMP and calcium spatiotemporal dynamics in developing neuronal circuits. Front CellNeurosci. 2014 Nov 13.

Nicol X, Hong KP, Spitzer NC. Spatial and temporal second messenger codes for growth cone turning. Proc Natl Acad Sci U S A.2011 Aug 16;108(33):13776-81.

Nicol X, Voyatzis S, Muzerelle A, Narboux-Nême N, Südhof TC, Miles R, Gaspar P. cAMP oscillations and retinal activity arepermissive for ephrin signaling during the establishment of the retinotopic map. Nat Neurosci. 2007 Mar;10(3):340-7.

Nicol X, Muzerelle A, Rio JP, Métin C, Gaspar P. Requirement of adenylate cyclase 1 for the ephrin-A5-dependent retraction ofexuberant retinal axons. J Neurosci. 2006 Jan 18;26(3):862-72.

Fields of research

Neurogenetics / neurodevelopment

Research Theme

The mature nervous system is an intricate network in which neurons are connected to specific partners. The choice of these partners is crucial for the correct behavior of the network (meaning the nervous system) and is determined at early stages of development. Abnormal development of neuronal connections is responsible for a large range of neuronal pathologies, some of them affecting vision. Research carried on by our team focuses on a better understanding of the development of sensory maps including the connection between the retina and the brain.

We aim to identify the codes of intracellular signals guiding retinal axons to the brain and shaping their arbors in their targets. We focus on signals required for axons to detect and interpret attractive and repulsive cues of axonal environment or involved in axonal and synaptic competition. Cyclic nucleotides and calcium are crucial for axons to integrate extracellular signals required for axon pathfinding and to modulate axonal and synaptic competition. They are involved in a wide range of other signaling pathways. We aim to decrypt the codes used by axons and synapses to identify such cellular messenger signals as specific regulators of neuronal connectivity.

We use a combination of anatomical, imaging and optogenetic techniques to investigate the role of second messengers in the development of sensory maps. FRET imaging enables following cellular messenger concentration in living cells. Other techniques including subcellular targeting of cAMP and calcium signaling blockers, and the use of light sensitive tools (optogenetics) make possible precise manipulations of these signals in time and space. Using these tools we are able to test the importance of local and temporal coding of cellular signals during the development of neuronal networks.

Project 1 : Spatiotemporal codes of second messengers for the development of neuronal connectivity. Second messengers modulate a wide range of cellular processes. We investigate the spatial and temporal features of cyclic nucleotide and calcium signals shaping neuronal connectivity to understand how second messengers achieve selectivity for their wide range of downstream pathways in developing axons.

Project 2 : Cooperation between neighboring axons to finely tune neuronal connectivity. Once axonal arbors are coarsely organized in their targets, complex and activity-dependent interactions between axons lead to the elimination of misplaced branches and synapses. This process requires interactions between neighboring axons. We aim to better understand these interactions between populations of axons.

Membres de l'équipe

Stefania Averaimo
Oriol Ros
Sandrine Couvet
Alice Louail
Solène Ribes

Lab rotation

Signaling signature of cellular processes shaping neuronal connectivity

Chercheur responsable: 

NICOL Xavier

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018 

~ April-June 2018

Project

Neuronal connectivity is shaped by the combination of progressive and regressive developmental processes. Pruning initially exuberant connections enables precise neuronal wiring and adaptation to the environment via mechanisms influencing developmental plasticity. 

The influence of individual guidance or adhesion cues on neuronal wiring has been elegantly described. However in vivo, axons are exposed to combinations of multiple cues. Recent evidence showed non-additive interactions amongst axon guidance factors. The mechanisms by which a neuron can integrate different signals to trigger stabilization or pruning of a defined axonal branch is unclear. Using subcellularly targeted FRET sensors, genetically-encoded buffers and optogenetic or chemogenetic actuators, we aim at identifying the signaling signature of retinal axon pruning.

Contact

Institut de la Vision - 17, rue Moreau 75012 Paris - +33 1 53 46 25 57 - Xavier.nicol@inserm.fr

Superviseur: 

NICOL Xavier & ROS Oriol