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Lab presentation

BUILDING A NERVOUS SYSTEM

Our team aims to understand the long road of building a nervous system. We focus on the smooth travels and the accidents on the journey to get the proper shape (a hollow neural tube), to acquire the proper size (control of tissue growth), and to the acquire the right types of cells (generation of cell diversity)

We study the neural tube, the early primordium of the building nervous system. We combine the use of animal models with human tissue engineering to understand the formation of the human brain and spinal cord in the embryo, as well as their developmental disorders

Projects

THE LONG ROAD OF BUILDING A NERVOUS SYSTEM, SMOOTH TRAVELS AND ACCIDENTS ON THE JOURNEY TO GET THE SHAPE

Our aim is to study the generation of the Secondary Neural Tube. Development of the posterior spinal cord involves the elongation of the body axis and the cavitation of the new structure in a poorly understood process called secondary neurulation. Importantly, accidents in this process are the cause of closed spina bifida, the most frequent neurodevelopmental malformation.

We are combining live imaging and data from transcriptomics and functional genetics, to unveil the gene regulatory networks and tissue dynamics of secondary neural tube formation.

Portada Thesis

THE LONG ROAD OF BUILDING A NERVOUS SYSTEM, SMOOTH TRAVELS AND ACCIDENTS ON THE JOURNEY TO GET THE SIZE

Our aim is to study the control of cell numbers and organ size at birth, as a model to study primary microcephalies. Tight control of the balance between specialized cell divisions is crucial to control the number of cells in the developing nervous system and the correct brain size at birth. Accidents in these processes result in primary microcephalies.

We demonstrated that growth factors (Sonic hedgehog, Shh, Wnt and BMP) signalling are required for the expansion of the pool of progenitors by maintaining symmetric divisions. By combining high resolution imaging, and data from transcriptomics and functional genetics, we aim to describe the mechanisms downstream growth factor activities that regulate neural stem cell maintenance

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THE LONG ROAD OF BUILDING A NERVOUS SYSTEM, LESSONS FROM EMBRYO DEVELOPMENT TO TISSUE/ORGAN ENGINEERING

Our aims is to engineered neural tube tissue (NT_Organoids) produced from human embryonic stem cells, to in vitro reconstitute the formation of the human nervous system primordium, and to be able, for the first time, to address fundamental questions related to building the human nervous system.

We are combining the generation of NT-Org, with live imaging and data from transcriptomics and functional genetics, to unveil the gene regulatory networks and tissue dynamics of human neural tube formation.

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Lab people

Senior Principal Investigator

Elisa Martí is a Research Professor at IBMB_CSIC. She has a long standing interest in Developmental Neurobiology, with the particular aim of understanding the formation of the Spinal Cord. She initiated her carrier in the field of Developmental Neurobiology as a doctorate student at the Royal Postgraduate Medical School (RPMS), London University and the University of La Laguna, Spain, were she set the grounds to identify patterns, conserved along evolution, for the generation of cell diversity in the developing Spinal Cord. During her postdoctoral training at Harvard University, she established the morphogenetic role of Sonic Hedgehog (Shh) in the generation of cell diversity in the developing Spinal Cord. These studies provided the foundations to establish her independent research group in Barcelona (IBMB-CSIC) in 2001. Her laboratory is internationally renowned for the work in genetic networks and cellular events that regulate Neural Development. She is particularly recognized for her extensive characterization of the Sonic Hedgehog pathway in neural development, but her research work has also extended to other signalling pathways (Wnt, BMP, TGFb).

She has contributed to scientific management at the IBMB as deputy director (2006-2009) and (2011-2014), and at the Spanish National Agency (AEI) as deputy in Neurobiology and Development (Fundamental and Systems Biology, BFS 2015-2018). She is a member of the Editorial Board of Developmental Neurobiology, and Frontiers in Cell and Developmental Biology.

Past students

Selected publications

Jose Blanco-Ameijeiras, Pilar Lozano-Fernandez, Elisa Marti (2021) Centrosome maturation: in tune with the cell cycle. J. Cell Science Jan 15;135(2):jcs259395. doi: 10.1242/jcs.259395. Epub 2022 Jan 28 https://pubmed.ncbi.nlm.nih.gov/35088834/


Elena Gonzalez-Gobartt, José Blanco-Ameijeiras, Susana Usieto, Guillaume Allio, Bertrand Bénazéraf and Elisa Martí (2021) Cell intercalation driven by SMAD3 underlies secondary neural tube formation Developmental Cell 56, 1147–1163 April 19, 2021 10.1016/j.devcel.2021.03.023 https://pubmed.ncbi.nlm.nih.gov/33878300/

Highlighted in Faculty Opinions https://facultyopinions.com/prime/739971343#eval793585539


Murielle Saade, Diego S Ferrero, José Blanco-Ameijeiras, Elena Gonzalez-Gobartt, Victor M Ruiz-Arroyo, Elena Martínez-Sáez, Santiago Ramón y Cajal, Nuria Verdaguer and Elisa Martí (2020) Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis. Cell Stem Cell 2020 Oct 27;S1934-5909(20)30496-3. doi: 10.1016/j.stem.2020.10.002. https://pubmed.ncbi.nlm.nih.gov/33147489/

Highlighted in Nature Review Microbiol https://www.nature.com/articles/s41579-020-00481-9


Gonzalez-Gobartt E, Allio G, Bénazéraf B, Martí Elisa (2020) In Vivo Analysis of the Mesenchymal-to-Epithelial Transition During Chick Secondary Neurulation. Methods Mol Biol. 2021; 2179:183-197. doi: 10.1007/978-1-0716-0779-4_16. https://link.springer.com/protocol/10.1007%2F978-1-0716-0779-4_16


Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto and Elisa Martí (2017) Shh-mediated centrosomal recruitment of PKA promotes symmetric proliferative neuroepithelial cell division. Nature Cell Biology 19, 493–503 (2017) doi:10.1038/ncb3512 http://www.nature.com/ncb/journal/v19/n5/abs/ncb3512.html

All publications

1.- Jose Blanco-Ameijeiras, Pilar Lozano-Fernandez, Elisa Marti (2021) Centrosome maturation: in tune with the cell cycle. J. Cell Science Jan 15;135(2):jcs259395. doi: 10.1242/jcs.259395. Epub 2022 Jan 28 https://pubmed.ncbi.nlm.nih.gov/35088834/


2.- Elena Gonzalez-Gobartt, José Blanco-Ameijeiras, Susana Usieto, Guillaume Allio, Bertrand Bénazéraf and Elisa Martí (2021) Cell intercalation driven by SMAD3 underlies secondary neural tube formation Developmental Cell 56, 1147–1163 April 19, 2021 10.1016/j.devcel.2021.03.023 https://pubmed.ncbi.nlm.nih.gov/33878300/

Highlighted in Faculty Opinions https://facultyopinions.com/prime/739971343#eval793585539


3.- Murielle Saade, Diego S Ferrero, José Blanco-Ameijeiras, Elena Gonzalez-Gobartt, Victor M Ruiz-Arroyo, Elena Martínez-Sáez, Santiago Ramón y Cajal, Nuria Verdaguer and Elisa Martí (2020) Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis. Cell Stem Cell 2020 Oct 27;S1934-5909(20)30496-3. doi: 10.1016/j.stem.2020.10.002. https://pubmed.ncbi.nlm.nih.gov/33147489/

Highlighted in Nature Review Microbiol https://www.nature.com/articles/s41579-020-00481-9


4.- Najas S, Pijuan I, Esteve-Codina A, Usieto S, Martinez JD, Zwijsen A, Arbonés ML, Martí E, Le Dréau G (2020) A SMAD1/5-YAP signalling module drives radial glia self-amplification and growth of the developing cerebral cortex.  Development. 2020 Jul 13;147(13): dev187005. doi: 10.1242/dev.187005 https://dev.biologists.org/content/147/13/dev187005


5.- Gonzalez-Gobartt E, Allio G, Bénazéraf B, Martí Elisa (2020) In Vivo Analysis of the Mesenchymal-to-Epithelial Transition During Chick Secondary Neurulation. Methods Mol Biol. 2021; 2179:183-197. doi: 10.1007/978-1-0716-0779-4_16. https://link.springer.com/protocol/10.1007%2F978-1-0716-0779-4_16


6.- Elena Garreta, Patricia Prado, Carolina Tarantino, Roger Oria, Lucia Fanlo, Elisa Martí, Dobryna Zalvidea, Xavier Trepat, Pere Roca-Cusachs, Aleix Gavaldà-Navarro, Luca Cozzuto, Josep Maria Campistol, Juan Carlos Izpisúa Belmonte, Carmen Hurtado del Pozo, Nuria Montserrat (2019) Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nature Materials Apr;18(4):397-405. doi: 10.1038/s41563-019-0287-6. https://www.nature.com/articles/s41563-019-0287-6


 7.- Murielle Saade, Jose Blanco-Ameijeiras, Elena Gonzalez-Gobartt, and Elisa Martí (2018) A centrosomal view of CNS growth  Development 145: dev170613 doi: 10.1242/dev.170613  http://dev.biologists.org/content/145/21/dev170613


8.- Gwenvael Le Dréau, René Escalona, Raquel Fueyo, Antonio Herrera, Juan D Martínez, Susana Usieto, Anghara Menendez, Sebastián Pons, Marian A Martinez-Balbas, and Elisa Marti (2018) E proteins sharpen neurogenesis by modulating proneural bHLH transcription factors activity in an E-box-dependent manner. Elife. 2018 Aug 10;7. pii: e37267. doi: 10.7554/eLife.37267 https://elifesciences.org/articles/37267

eLife Digest https://doi.org/10.7554/eLife.37267.002


9.- Kim Dale and Elisa Martí (2017) Introduction to the special section of YDBIO on: Spinal cord a model to understand CNS development and regeneration. Dev Biol. 2017 Dec 1;432(1):1-2. doi: 10.1016/j.ydbio.2017.10.005. Epub 2017 Oct 13 http://www.sciencedirect.com/science/article/pii/S0012160617307170?via%3Dihub

cover caption http://www.sciencedirect.com/journal/developmental-biology/vol/432/issue/1


10.- Demian Burguera , Yamile Marquez , Claudia Racioppi , Jon Permanyer , Antonio Torres, Rosaria Esposito, Beatriz Albuixech , Lucía Fanlo , Ylenia d’Agostino , Enrique Navas-Perez , Ana RiesgY, Claudia Cuomo , Giovanna Benvenuto, Lionel A. Christiaen, Elisa Martí, Salvatore D’Aniello, Antonietta Spagnuolo, Filomena Ristoratore, Maria Ina Arnone, Jordi Garcia-Fernàndez, Manuel Irimia (2017) Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes. Nat Commun. 2017 Nov 27;8(1):1799. doi: 10.1038/s41467-017-01961-y. https://www.nature.com/articles/s41467-017-01961-y


11.- Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto and Elisa Martí (2017) Shh-mediated centrosomal recruitment of PKA promotes symmetric proliferative neuroepithelial cell division. Nature Cell Biology 19, 493–503 (2017) doi:10.1038/ncb3512 http://www.nature.com/ncb/journal/v19/n5/abs/ncb3512.html


12.- M Angeles Rabadán, Antonio Herrera, Lucia Fanlo, Susana Usieto, Carlos Carmona-Fontaine, Elias H. Barriga, Roberto Mayor, Sebastián Pons and Elisa Martí (2016) Delamination of neural crest cells requires transient and reversible Wnt inhibition mediated by DACT1/2  2   Development  143(12):2194-205. doi: 10.1242/dev.134981 http://dev.biologists.org/content/143/12/2194.long


13.- Jo Richardson, Anton Gauert, Luis Briones Montecinos, Lucía Fanlo Escudero, Alhashem Zainalabdeen, Elisa Martí, Alexandre Kabla, Steffen Härtel and Claudia Linker (2016) Leader cells define directionality of trunk, but not cranial, neural crest migration. Cell Reports 15(9):2076-88. doi: 10.1016/j.celrep.2016.04.067 http://www.sciencedirect.com/science/article/pii/S2211124716305113


14.- Serena Mirra, Fausto Ulloa, Irene Gutierrez-Vallejo, Elisa Martì, and Eduardo Soriano (2016) Function of Armcx3 and Arm10/SVH genes in the regulation of progenitor proliferation and neural differentiation in the chicken spinal cord. Front Cell Neurosci  Mar 3;10:47  doi: 10.3389/fncel.2016.00047. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776218/pdf/fncel-10-00047.pdf


15.- Antonio Herrera, Murielle Saade, Anghara Menendez, Elisa Marti and Sebastian Pons (2014) Pre-neoplastic growth caused by sustained Wnt/β-Catenin depends on the localization and activation of aPKC at the apical pole of neuroepithelial cells. Nat Commun  5:4168. doi: 10.1038/ncomms5168. http://www.ncbi.nlm.nih.gov/pubmed/24942669


16.- Gwenvael Le Dréau, Murielle Saade, Irene Gutierrez-Vallejo and Elisa Martí (2014) The strength of SMAD1/5 activity determines stem cell fate in the developing spinal cord. J Cell Biol.  204 (4) 591-605)  doi: 10.1083/jcb.201307031

Cover picture http://jcb.rupress.org/content/204/4.cover.pdf

Highlighted in JCB, “Career guidance for stem cellsJ Cell Biol 2014 204:463.  doi:10.1083/jcb.2044if http://jcb.rupress.org/content/204/4/591.abstract


17.- Murielle Saade, Irene Gutierrez, Gwenvael Le Dreau, M Angeles Rabadán, David G. Miguez, Javier Buceta and Elisa Martí (2013) Sonic hedgehog signaling switches the mode of division in the developing nervous system. Cell Reports 4(3):492-503. doi: 10.1016/j.celrep.2013.06.038.

Highlighted in F1000  http://f1000.com/prime/718050366#recommendations-content

http://www.ncbi.nlm.nih.gov/pubmed/23891002


18.- Tiago Ferronha, M Angeles Rabadán, Estel Gil-Guiñón, Gwenvael LeDreau, Carmen deTorres and Elisa Martí  (2013) LMO4 is an essential cofactor in the Snail2-mediated epithelial-to-mesenchymal transition of neuroblastoma and neural crest cells. Journal of Neuroscience 33(7):2794-2806; doi:10.1523/JNEUROSCI.4062-12.2013  http://www.ncbi.nlm.nih.gov/pubmed/23407937


19.- Angeles Rabadán, Jordi Cayuso, Gwenvael Le Dreau, Catarina Cruz, Mercedes Barzi, Sebastián Pons, James Briscoe and Elisa Martí (2012) Jagged2 controls the switch between motor neuron and oligodendrocyte generation in the spinal cord. Cell Death and Differentiation 19(2):209-19 (2012) http://www.ncbi.nlm.nih.gov/pubmed/21720386


20.- Gwenvael Le Dréau, Lidia Garcia-Campmany, Angeles Rabadán, Tiago Ferronha, Samuel Tozer, James Briscoe and Elisa Martí (2012) Canonical BMP7 activity is required for the generation of discrete neuronal populations in the dorsal spinal cord. Development 139(2):259-68 (2012) http://www.ncbi.nlm.nih.gov/pubmed/22159578

Cover Picture http://dev.biologists.org/content/139/2.cover-expansion


21.- Roberto Alvarez-Medina, Gwenvael Le Dreau, Marian Ros and Elisa Martí (2009) Hedgehog activation is required upstream of Wnt signalling to control neural progenitor proliferation. Development 136(19):3301-3309 (2009)

Highlighted in Development, 136 “Multitasking Wnts in neural development” http://dev.biologists.org/content/136/19/e1904.full


22.- Roberto Alvarez-Medina, Jordi Cayuso, Tadashi Okubo, Shinji Takada and Elisa Martí (2008). Wnt canonical pathway restricts graded Shh/Gli patterning activity through the regulation of Gli3 expression. Development 135, 237-247 (2008) www.ncbi.nlm.nih.gov/pubmed/18057099

Cover Picture http://dev.biologists.org/content/135/2.cover-expansion

Highlighted in Development 2008, 135: 202 “Wnt-Shh neural tube patterning crosstalk” http://dev.biologists.org/content/135/2/e202.full

Project funding

FUNDING FROM THE LAST 10 YEARS

1.- REF: PID2019-104134GB-I00 UNDERSTANDING THE MOLECULAR MECHANISMS REGULATING EMBRYONIC GROWTH OF THE CENTRAL NERVOUS SYSTEM IP Elisa Martí Gorostiza

2.- REF: MaratoTV3_2018 “DE L’ESTRUCTURA ALS MECANISMES PELS QUALS EL VIRUS ZIKA PROVOCA NEUROPATIES CONGÉNITES” IP; Nuria Verdaguez (co-IP Elisa Martí Gorostiza)

3.- REF RED2018-102553-T REDEVNEURAL 3.0: UN ENFOQUE INTEGRADOR PARA ENTENDER LA LOGICA DEL DESARROLLO NEURAL” IP Elisa Martí Gorostiza (coordinadora; Paola Bovolenta CBMSO-CSIC)

4.- REF BFU2016-77498-P “CONTROL GENETICO DELA FORMACION Y CRECIMIENTO DE LA MEDULA ESPINAL, UN MODELO PARA ESTUDIAR DEFECTOS DEL NEURODESARROLLO” IP: Elisa Martí Gorostiza

5.- REF AECC Cancer Infantil 2016 “CARACTERIZACIÓN DEL SISTEMA NXPH/NRXN COMO MARCADOR DE CELULAS MADRE DE NEUROBLASTOMA Y POSIBLE DIANA TERAPEUTICA” IP: Elisa Martí Gorostiza

6.- REF: BFU2016-81887-REDT: “REDEVNEURAL: UN ENFOQUE INTEGRADOR PARA ENTENDER LA LOGICA DEL DESARROLLO NEURAL” IP Elisa Martí Gorostiza (coordinadora; Paola Bovolenta CBMSO-CSIC)

7.-  REF: BFU2013-46477-P “DESARROLLO DE LA MEDULA ESPINAL, UN MODELO PARA ESTUDIAR FORMACION DE ORGANOS, BIOLOGIA DE CELULAS MADRE Y TRANSICION EPITELIO MESENQUIMA”. IP Elisa Martí Gorostiza

8.- REF: BFU2014-55738-REDT “GENERANDO DIVERSIDAD NEURAL” IP Elisa Martí Gorostiza (Coordinadora: Paola Bovolenta, CBMSO-CSIC) 32.000€

9.-  REF: BFU2010-18959 “DESARROLLO TEMPRANO DEL SISTEMA NERVIOSO DE VERTEBRADOS CONTROL GENETICO DE LA IDENTIDAD Y LA MORFOLOGIA CELULAR” IP Elisa Martí Gorostiza

Vacancies/Jobs

We’re building a multidisciplinary and enthusiastic group of scientists. We are seeking candidates having a strong background in bioinformatics, or human stem cell reprogramming, and/or developmental biology, to apply for upcoming calls for international postdoctoral fellowships (EMBO and Marie-Curie), and from the Spanish Government (Juan de la Cierva),

Please contact us directly to the following email address:
MURIELLE msabmc@ibmb.csic.es
ELISA emgbmc@ibmb.csic.es
the sooner the better!

We always look for talented undergraduate and graduate students for internships, short-term visits and long-term projects.

Lab corner

Highlighted

Early-Career Researchers in the Time of COVID-19
(DOI: https://doi.org/10.1016/j.stem.2021.01.012).

Past webinars videos

Recent Meetings

Social Life In/Out of the Lab

Celebrating March 8th 2022

Celebrating Sant Jordi, April 23rd 2021

Celebrating Masters Degrees, June 2021

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