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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
- Multiple parallel cell lineages in the developing mammalian cerebral cortex. Del-Valle-Anton L, Amin S, Cimino D, Neuhaus F, Dvoretskova E, Fernández V, Babal YK, Garcia-Frigola C, Prieto-Colomina A, Murcia-Ramón R, Nomura Y, Cárdenas A, Feng C, Moreno-Bravo, J.A, Götz, M, Mayer C and Borrell V. Science Advances. 2024 10 (13), eadn9998 https://doi.org/10.1126/sciadv.adn9998
- Input-dependent segregation of visual and somatosensory circuits in the mouse superior colliculus Teresa Guillamón-Vivancos, Mar Aníbal-Martínez, Lorenzo Puche-Aroca, Juan Antonio Moreno-Bravo, Miguel Valdeolmillos, Francisco J. Martini, Guillermina López-Bendito Science 2022 Aug 19; 377(6608):845-850 https://doi.org/10.1126/science.abq2960
- Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons Company V, Andreu-Cervera A, Madrigal MP, Andrés B, Almagro-García F, Chédotal A, López-Bendito G, Martinez S, Echevarría D, Moreno-Bravo JA, Puelles E Front Cell Dev Biol 2021 9:682067 https://doi.org/10.3389/fcell.2021.682067
- 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
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- Multiple parallel cell lineages in the developing mammalian cerebral cortex. Del-Valle-Anton L, Amin S, Cimino D, Neuhaus F, Dvoretskova E, Fernández V, Babal YK, Garcia-Frigola C, Prieto-Colomina A, Murcia-Ramón R, Nomura Y, Cárdenas A, Feng C, Moreno-Bravo, J.A, Götz, M, Mayer C and Borrell V. Science Advances. 2024 10 (13), eadn9998 https://doi.org/10.1126/sciadv.adn9998
- Rnd3 is necessary for the correct oligodendrocyte differentiation and myelination in the central nervous system. Madrigal MP, Ballester-Lurbe B, Gómez O, Moreno-Bravo JA, Puelles E, Jurado S, Garcia-Verdugo JM, Pérez-Roger I, Terrado J Brain Struct Funct. 2022 227(3): 829-841 https://doi.org/10.1007/s00429-021-02419-0
- Gli2-Mediated Shh Signaling Is Required for Thalamocortical Projection Guidance Callejas-Marin A, Moreno-Bravo JA, Company V, Madrigal MP, Almagro-García F, Martínez S, Puelles E Frontiers in Neuroanatomy 2022 16: 830758 http://doi.org/10.3389/fnana.2022.830758
- Input-dependent segregation of visual and somatosensory circuits in the mouse superior colliculus Teresa Guillamón-Vivancos, Mar Aníbal-Martínez, Lorenzo Puche-Aroca, Juan Antonio Moreno-Bravo, Miguel Valdeolmillos, Francisco J. Martini, Guillermina López-Bendito Science 2022 Aug 19; 377(6608):845-850 https://doi.org/10.1126/science.abq2960
- Uncoupling axon guidance and neuronal migration in Robo3-deficient inferior olivary neurons. Moreno Bravo, J.A., Rappeneau, Q., Roig-Puiggros, S., Sotelo, C., Chédotal, A. J Comp Neurol. 2022 530(16): 2868-2880 https://doi.org/10.1002/cne.25381
- Netrin 1-Mediated Role of the Substantia Nigra Pars Compacta and Ventral Tegmental Area in the Guidance of the Medial Habenular Axons Company V, Andreu-Cervera A, Madrigal MP, Andrés B, Almagro-García F, Chédotal A, López-Bendito G, Martinez S, Echevarría D, Moreno-Bravo JA, Puelles E Front Cell Dev Biol 2021 9:682067 https://doi.org/10.3389/fcell.2021.682067
- Loss of floor plate netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements Pourchet O, Morel MP, Welniarz Q, Sarrazin N, Marti F, Heck N, Gallea C, Doulazmi M, Roig Puiggros S, Moreno-Bravo JA, Vidailhet M, Trembleau A, Faure P, Chedotal A, Roze E, Dusart I Cell Reports 2021 34(3): 108654 http://doi.org/10.1016/j.celrep.2020.108654
- 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
- The amniote oculomotor complex Company V, Moreno-Bravo JA, Perez-Balaguer A, Puelles E Anatomical Record 2019 302(3):446 https://doi.org/10.1002/ar.23827
- Long-Range Guidance of Spinal Commissural Axons by Netrin1 and Sonic Hedgehog from Midline Floor Plate Cells Wu Z, Makihara S, Yam PT, Teo S, Renier N, Balekoglu N, Moreno-Bravo JA, Olsen O, Chedotal A, Charron F, Tessier-Lavigne M Neuron 2019 101(4): 635-647.e4 http://doi.org/10.1016/j.neuron.2018.12.025
- 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
- Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain Albuixech-Crespo B, Lopez-Blanch L, Burguera D, Maeso I, Sanchez-Arrones L, Moreno-Bravo JA, Somorjai I, Pascual-Anaya J, Puelles E, Bovolenta P, Garcia-Fernàndez J, Puelles L, Irimia M, Ferran JL PLoS Biol 2017 15(4):e2001573 https://doi.org/10.1371/journal.pbio.2001573
- Developmental guidance of the retroflex tract at its bending point involves Robo1-Slit2-mediated floor plate repulsion Moreno-Bravo JA, Martinez-Lopez JE, Madrigal MP, Kim M, Mastick GS, Lopez-Bendito G, Martinez S, Puelles E Brain Struct Funct 2016 221(1):665 https://doi.org/10.1007/s00429-014-0932-4
- Mesencephalic origin of the rostral Substantia nigra pars reticulata Madrigal MP, Moreno-Bravo JA, Martinez-Lopez JE, Martinez S, Puelles E Brain Struct Funct 2016 221(3):1403 https://doi.org/10.1007/s00429-014-0980-9
- Mesencephalic basolateral domain specification is dependent on Sonic Hedgehog Martinez-Lopez JE, Moreno-Bravo JA, Madrigal MP, Martinez S, Puelles E Front Neuroanat 2015 9:12 https://doi.org/10.3389/fnen.2015.00012
- Growth and differentiation factor 10 (Gdf10) is involved in Bergmann glial cell development under Shh regulation Mecklenburg N, Martinez-Lopez JE, Moreno-Bravo JA, Perez-Balaguer A, Puelles E, Martinez S Glia 2014 62(10):1713 https://doi.org/10.1002/glia.22710
- Role of Shh in the development of molecularly characterized tegmental nuclei in mouse rhombomere 1 Moreno-Bravo JA, Perez-Balaguer A, Martinez-Lopez JE, Aroca P, Puelles L, Martinez S, Puelles E Brain Struct Funct 2014 219(3):777 https://doi.org/10.1007/s00429-013-0534-6
- Mesencephalic neuronal populations New insights on the ventral differentiation programs Moreno-Bravo JA, Martinez-Lopez JE, Puelles E Histol Histopath 2012 27(12):1529
