Topic: Development, Evolution and Function of Commissural Systems

Speaker: Alain Chédotal, Ph.D.(UPMC Unniversity)

Time: 13:00-15:00, Tue, May 8th, 2018

Location: #1113, Wangkezhen Building, Peking University

Host: Prof. Yi Rao

Abstract: 

In most animal species including humans, commissural axons connect neurons on the left and right side of the nervous system. This communication between the two sides of the brain and spinal cord is necessary for a series of complex function, including binocular vision, coordinated locomotor movements, and sound direction localization. In humans, the balance of commissural and non-commissural axons is essential to CNS physiology and to the integration of sensory stimuli/inputs. Abnormal axon midline crossing during development causes a whole range of neurological disorders ranging from congenital mirror movements, horizontal gaze palsy, scoliosis or binocular vision deficits. Partial or complete corpus callosum agenesis are some of the most common brain malformations in children with variable neurological outcomes. I will discuss some of the genetic mechanisms underlying anomalies of midline crossing and present some of our most recent work that challenges the existing dogmas and suggest that commissural axon guidance mechanisms are more diverse across species than previously appreciated. To facilitate the analysis of the organization and evolution of commissural systems in vertebrates, we have developed a new imaging method which combines whole-mount immunostaining or commissural axon tracing, tissue clearing with organic solvents and 3D light-sheet microscopy. I will also present some applications of this method in the field of human embryology and our ongoing effort to generate a database and cell atlas of the developing human embryo, normal or pathologic. 

Selected publications 

Dominici C., Moreno-Bravo, J.A., Roig Puiggros, S., Rappeneau, Q., Rama, N., Vieugue, P., Bernet, A., Mehlen, P.* and Chédotal A. (2017) Floor plate-derived Netrin-1 is dispensable for commissural axon guidance. Nature 544:350-354. 

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.

 Rama, N., Dubrac, A., Mathivet, T., Ni-Charthaigh, R.A., Genet, G., Cristofaro, B., Pibouin-Fragner, L., Ma, L., Eichmann, A. and Chédotal, A. (2015) Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization. Nature Medicine, 21:483-491.

Zelina, P., Blockus, H., Zagar, Y., Peres, A., Friocourt, F., Wu, Z. H., Rama, N., Fouquet, C., Hohenester, E., Tessier-Lavigne, M., Schweitzer, J., Crollius, H. R. and Chédotal, A. (2014) Signaling Switch of the Axon Guidance Receptor Robo3 during Vertebrate Evolution. Neuron 84: 1258-1272.

 Bouvier, J., Thoby-Brisson, M., Renier, N., Dubreuil, V., Ericson, J., Champagnat, J., Pierani,* A., Chédotal, A*. and Fortin, G*. (2010) Hindbrain interneurons and axon guidance signaling critical for breathing. Nature Neuroscience 13: 1066-1074. *Co-corresponding authors.