Development, Wiring and Function of Cerebellar Circuits

Lines of investigation

The goal of the lab is understanding how early alterations of the cerebellum are related to diverse neurodevelopmental disorders. The questions we pursue are grounded in determine, from a developmental perspective, how cerebellar abnormalities impact on the brain function.

We combine mouse genetics to develop animal models with cerebellar alterations, state-of-the-art histological, cellular, molecular biology methods and techniques, transcriptomics and functional analyses.

Our ultimate goal is to understand the contribution of the cerebellum to cognition in both typical development and developmental disorders and to translate this knowledge into clinical applications.

Our research is focused in two main research lines:

-Understanding cerebellar long-range connectivity that relays cerebellar output to diverse brain areas. We aim to elucidate how the cerebellum influences the development and function of remote brain circuits, with particular interest on the cerebellar modulation of the developing cortical circuits.

-Investigating the development and assembly of local cerebellar circuits. We seek to determine basic regulatory mechanisms underlying the formation and function of these circuit and how alterations in these processes derive in an abnormal function of the cerebellum.

Representative Publications

Neural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold Kaur N* , Han W*, Li Z*, Madrigal MP, Shim S, Pochareddy S, Gulden FO, Li M, Xu X, Xing X, Takeo Y, Li Z, Lu K, Imamura Kawasawa Y, Ballester-Lurbe B, Moreno-Bravo JA, Chédotal A, Terrado J, Pérez-Roger I, Koleske AJ, Sestan N. Neuron 2020 107(6): P1197 https://doi.org/10.1016/j.neuron.2020.06.035
Remotely Produced and Axon-Derived Netrin-1 Instructs GABAergic Neuron Migration and Dopaminergic Substantia Nigra Development Brignani S* , Raj DA*, Schmidt ER, Düdükcü Ö, Adolfs Y, De Ruiter A, Rybiczka-Tesulov M, Verhagen M, van der Meer C, Broekhoven M, Moreno-Bravo JA, Grossouw L, Dumontier E, Cloutier JF, Chédotal A, Pasterkamp RJ Neuron 2020 107(4): P684 https://doi.org/10.1016/j.neuron.2020.05.037
Synergistic Activity of Floor-Plate- and Ventricular-Zone-Derived Netrin-1 in Spinal Cord Commissural Axon Guidance Moreno-Bravo JA* , Roig Puiggros S*, Mehlen P, Chédotal A Neuron 2019 101(4): P625 https://doi.org/10.1016/j.neuron.2018.12.024
Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin 1 Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Heike Blockus, Chloé Dominici, Pavol Zelina, Patrick Mehlen, Alain Chédota Development 2018 145 (2): dev159400 https://doi.org/10.1242/dev.159400
Floor-plate-derived netrin-1 is dispensable for commissural axon guidance Chloé Dominici, Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Quentin Rappeneau, Nicolas Rama, Pauline Vieugue, Agns Bernet, Patrick Mehlen & Alain Chédotal Nature 2017 545: 350 https://doi.org/10.1038/nature22331

See all

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Main Investigator