Netrin-1 derived from the vertebrate midline had far been widely accepted as the textbook example of chemotropic long-range attraction. We showed that netrin-1 from neural progenitors and not floor plate cells, is responsible for attracting hindbrain commissural axons towards the ventral midline ¹. Our data suggested that netrin-1 is acting as a “short-range” cue promoting growth cone adhesion along the pial surface of the brain. These results present a major shift in thinking about the classical principles of axon guidance mechanisms and are proving to be a major turning point in the field ^{2 3}.

Furthermore, I worked on understanding the implication of netrin-1 in the cerebellar wiring.The alteration of netrin-1 signalling in the cerebellum leads to abnormal behaviors that could be related to autism-like symptoms. Hence, my interests grew in understanding how the cerebellum was implicated in these dysfunctions.

The anatomical substrate by which the cerebellum could contribute to these behaviors is the cerebello-thalamo-cortical pathway. Therefore, I have been studying the spatiotemporal window in which the cerebellum could influence the development of the thalamocortical network.

I plan to integrate basic aspects about cerebellar development with functional aspects of the thalamocortical system to shed light on the cerebellar origin of high-order deficits.

References:

¹ Dominici C^*, Moreno-Bravo J.A.^*, Puiggros SR, Rappeneau Q, Rama N, Vieugue P, Bernet A, Mehlen P, Chédotal A. (2017). Floor-plate-derived netrin-1 is dispensable for commissural axon guidance. Nature. 2017 May 18; 545 (7654): 350-354. doi: 10.1038/nature22331. ^*Equal contribution. Highlighted in F1000Prime. Preview in Neuron
² Moreno-Bravo J.A.^*, Puiggros SR^*, Blockus H, Dominici C, Zelina P, Mehlen P, Chédotal A (2018). Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zonederived netrin-1. Development. Jan 17; 145 (2). pii: dev159400. doi: 10.1242/dev.159400. ^*Equal contribution
³ Moreno-Bravo J.A.^*, Roig Puiggros S^*, Mehlen P, Chédotal A. Synergistic Activity of Floor-Plate-and-Ventricular-Zone-Derived Netrin-1 in Spinal Cord Commissural Axon Guidance. Neuron. 2019 Feb 20; 101 (4): 625-634.e3. doi:10.1016/j.neuron.2018.12.024. ^*Equal contribution