Neurogenetics of Locomotion

Our research aims to understand the mechanisms, genes and circuits that govern coordinated locomotion under normal and anomalous or pathological conditions.

Behaviorally, we intend to understand how the ensemble of sensory circuits, central pattern generators, motor neurons and higher order centers collectively interact in order to optimize locomotion under different settings, including pathological conditions.

For this we use the genetically tractable model system Drosophila melanogaster, which combines powerful genetic tools with sophisticated and detailed kinematic quantification approaches. Considering how motor systems and the genes that define them are evolutionarily conserved, this work will impact the study of motor control of more complex organisms and contribute to the study of human motor conditions. Moreover, the tools and approaches we use can easily be translated into more complex organism including rodents and humans. 

Graphical Abstract

MouseWalker

The MouseWalker is an open-source, integrated hardware and software system that provides a comprehensive and quantitative description of kinematic features in freely walking rodents.

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"A Genetic model for neurorehabilitation” PTDC/BIA-COM/0151/2020, Foundation for Science and Technology (FCT), Principal investigator

“Senescent cells and their secretory phenotype: novel targets for spinal cord repair” -MC-36-2020 Prémio Melo e Castro 2020, Santa Casa da Misericórdia de Lisboa; Partener (Principal investigator: Leonor Saúde, iMM)

"Development of an inexpensive, simple and open-source device for SARS-Cov-2 detection." Projetos de implementação rápida para soluções inovadoras - COVID-19, #613788604; Foundation for Science and Technology (FCT). Principal investigator

“Testing the protective effect of candidate compounds in a Drosophila model of Amyotrophic Lateral  Sclerosis (ALS)”, iNOVA4Health, UNL; Co- Principal investigator (with Claudia Santos, ITQB)

"A Genetic model for neurorehabilitation" H2020-MSCA-IF-2016, #752891 Marie Skłodowska-Curie program –Reintegration Grant-; European Commission. Principal investigator

“Neurogenetics of Locomotion” Investigator FCT; IF/01154/2014/CP1252/CT0003, Foundation for Science and Technology (FCT), Principal investigator

  • D Carregosa, N Loncarevic-Vasiljkovic, R Feliciano, D Moura-Louro, CS Mendes, CN dos Santos (2024) “Locomotor and gait changes in the LPS model of neuroinflammation are correlated with inflammatory cytokines in blood and brain” Journal of Inflammation 21 (1), 39
  • AM Medeiros, AF Hobbiss, G Borges, M Moita, CS Mendes (2024) “Mechanosensory bristles mediate avoidance behavior by triggering sustained local motor activity in Drosophila melanogaster” Current Biology 34 (13), 2812
  • AR Fernandes, JP Martins, ER Gomes, CS Mendes, RO Teodoro (2023) “Drosophila motor neuron boutons remodel through membrane blebbing coupled with muscle contraction” Nature Communications 14 (1), 3352
  • R Rosado-Ramos, GM Poças, D Marques, A Foito, DM Sevillano, M Lopes-da-Silva, LG Gonçalves, R Menezes, M Ottens, D Stewart, A Ibáñez de Opakua, M Zweckstetter, MC Seabra, CS Mendes, TF Outeiro, PM Domingos, CN Santos (2023) “Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage” Nature Communications 14 (1), 1918
  • AF Isidro, AM Medeiros, I Martins, D Neves-Silva (2023) “Using the MouseWalker to quantify locomotor dysfunction in a mouse model of spinal cord injury” J Vis Exp 193, e65207
  • [preprint] AM Medeiros, AF Hobbiss, G Borges, M Moita, CS Mendes “Mechanosensory stimulation triggers sustained local motor activity in Drosophila melanogaster” bioRxiv, 2022.07. 19.500315
  • [preprint] A Cabrita, AM Medeiros, T Pereira, AS Rodrigues, M Kranendonk, CS Mendes, (2022) “Motor dysfunction in Drosophila melanogaster as a biomarker for developmental neurotoxicity” 15 Jul 2022, In: iScience. 25, 7, p. 104541; bioRxiv 2021.07.09.451676.
  • [preprint] A Cabrita, AM Medeiros, T Pereira, AS Rodrigues, M Kranendonk, CS Mendes (2021) “Motor dysfunction in Drosophila melanogaster as a biomarker for developmental neurotoxicity” bioRxiv 2021.07.09.451676
  • Sardoo A, Neto A, Torres RP, Rodrigues-Manica S, Domingues L, Crespo CL, Lagoas-Gomes J, Mascarenhas V, Mendes CS, Galzerano A, Almeida SFd, Sepriano A, Ramiro S, Masi A, Nair K, Costa J, Alexandre B, Vassilevskaia T, Cunha C, Sobral D, Branco J, Gomes-Alves P, Pimentel-Santos F. (2021) “The role of muscle in the susceptibility and progression of axial Spondyloarthritis: The MyoSpA Study Protocol”, Acta Reumatol Port. Oct-Dec 2021;46(4):342-349.
  • [preprint] AR Fernandes, CS Mendes, ER Gomes, RO Teodoro, (2021) “Motor neuron boutons remodel through membrane blebbing” bioRxiv 2021.03.07.434250
  • F Heredia, Y Volonté, J Pereirinha, M Fernandez-Acosta, AP Casimiro, CG Belém, F Viegas, K Tanaka, J Menezes, M Arana, G A. Cardoso, A Macedo, M Kotowicz, F H. Prado Spalm, MJ Dibo, RD Monfardini, TT Torres, CS Mendes, A Garelli, AM Gontijo (2021) “Innate Behavior Sequence Progression by Peptide-Mediated Interorgan Crosstalk” Nature Communications, 07 June 2021
  • S Skarlatou,; C Hérent; E Toscano; CS Mendes; J Bouvier; N Zampieri. "Afadin Signaling at the Spinal Neuroepithelium Regulates Central Canal Formation and Gait Selection". Cell Reports 31 10 (2020): 107741.
  • CS Mendes*, I Bartos, Z Márka, T Akay, S Márka, RS Mann*. (2015) “Quantification of gait parameters in freely walking rodents”. BMC Biology, 22 July, 13:50. * corresponding authors.
  • MB Bouchard, V Voleti, CS Mendes, C Lacefield, WB Grueber, RS Mann, RM Bruno and EMC Hillman, (2015) “Swept Light Sheet (SLS) imaging for ultra-fast, volumetric microscopy in awake, behaving organisms”, Nature Photonics, Feb;9(2):113-119 (cover article).
  • CS Mendes*, SV Rajendren, I Bartos, S Márka, RS Mann*. (2014) “Kinematic responses to changes in walking orientation and gravitational load in Drosophila melanogaster”, PLoS ONE 9(10): e109204. * corresponding authors. 
  • CS Mendes, I Bartos, T Akay, S Márka, RS Mann. (2013) “Quantification of gait parameters in freely walking wild type and sensory deprived Drosophila melanogaster”. eLife, January 8.
  • CS Mendes, C Levet , G Chatelain, P Dourlen, A Fouillet, ML Dichtel-Danjoy, A Gambis, HD Ryoo, H Steller, B Mollereau. (2009) “ER stress protects from retinal degeneration.” The EMBO Journal ;28(9):1296-307.
  • CS Mendes, E Arama, S Brown, H Scherr, M Srivastava, A Bergmann, H Steller, B Mollereau (2006) “Cytochrome-c-d regulates developmental apoptosis in the Drosophila retina” EMBO reports ;7(9):933-9 (cover article).
  • RD Almeida, BJ Manadas, CV Melo, JR Gomes, CS Mendes, MM Grãos, RF Carvalho, AP Carvalho and CB Duarte (2005) “Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways” Cell Death and Differentiation 12: 1329–1343
  • PM Domingos, M Mlodzik, CS Mendes, S Brown, H Steller, B Mollereau (2004) “Spalt transcription factors are required for R3/R4 specification and establishment of planar cell polarity in the Drosophila eye.” Development. 131(22):5695-702. 

2021, Best poster, Portuguese Drosophila meeting (to Anna Hobbiss)
2020, Best talk, Portuguese Drosophila meeting (to Anna Hobbiss)
2019, Best Basic Research Talk - iMed Innovate Competition (to Ricardo Custódio)
2017, Marie Sklodowska-Curie program, Reintegration Grant
2014, FCT investigator, Starting Grant
2014, Drosophila Image Award, runner up, Genetics Society of America
2011, Travel grant, XII Portuguese Society for Neuroscience Meeting

NMS Research promotes brain science literacy among youth and seniors

To observe the Brain Awareness Week, NMS organized two neuroscience fairs in two schools in Lisbon and one "pop-up" science center at Museu da Saúde, between March 13th and 17th.

  • Alisson Gontijo, NMS
  • Cláudia Santos, NMS
  • Fernando Pimentel-Santos, NMS
  • Hugo Miranda, NMS
  • Leonor Saúde, iMM 
  • Marta Moita, CCU 
  • Michel Kranendonk, NMS 
  • Niccolo Zampieri, Max-Delbrück-Centrum for Molecular Medicine, Germany 
  • Rita Teodoro, NMS
  • Sandra Tenreiro, NMS
  • Sebastião Rodrigues, NMS
  • Vasco Barreto, FCT NOVA

Principal Investigator

César Mendes

Team

Anna Hobbiss
Post-Doc Researcher
Ana Colaço
PhD Student
Margarida Brotas
PhD Student
Nuno Cristino
PhD Student
Mafalda Lontrão
Msc Student
Márcia Fontes
PhD Student