Development of the Vertebrate Central Nervous System

PUJADES group   http://pujadeslab.upf.edu

Cristina Pujades, Group Leader

Sylvia Dyballa, Postdoctoral Fellow

Covadonga Fernández, Postdoctoral Fellow

Christian Cortés, Postdoctoral Fellow

Adrià Voltes, PhD student

Ivan Belzunce, PhD student

Carla Belmonte, PhD Student

SCIENTIFIC INTERESTS

A long-standing goal of developmental biology is to understand how multiple cell types are generated and maintained in highly organized spatial patterns. Our group explores the mechanisms underlying the organization of cells into highly developed structures in the Nervous System, with special attention to the patterning of cell lineages. We want to address three fundamental questions in neural development: i) how cell diversity is generated from single precursors (cell lineage reconstruction); ii) how cell fate decisions are taken and regulated; and iii) how cell fate affects cell behavior. We tackle these questions in two structures, which are interconnected by neuronal circuits: the hindbrain and the inner ear. At the end we want to understand how sensory inputs from the inner ear are conveyed and relayed into the hindbrain, and how neural circuits are then established within the brain. We use zebrafish embryos as model system because permits functional genetic studies to be combined with 3D+time in vivo imaging.

Our current projects are the following:

  1. Global cell lineage reconstitution of the otic vesicle during early embryonic development. Our aim is to generate the complete lineage tree of the neurosensory elements of the inner ear by high spatial and temporal resolution 2-photon 3D+time imaging. We correlate the progenitor potentials to the temporal and spatial proneural gene requirements.
  2. Deciphering the topographical representation of the sensory information at central levels. We investigate the selective innervation of hindbrain regions by somatosensory afferents and the gene requirements. An extended goal is the study of how changes or variations in the behavior are reflected in the underlying neuronal activity and perform brain-wide neuronal dynamics in response to sensory stimuli.
  3. Understanding morphomechanics during hindbrain segmentation. We have recently shown the role of actomyosin cables acting downstream of EphA/Ephrin signaling in the segregation of rhombomeric cell populations. We are currently exploring the cellular machinery and the molecular players responsible of the assembly of the mechanical barrier.
  4. Exploring the fate of the Boundary Cell Population (BCP). The BCP is generated at interface between two rhombomeres, and displays a specific gene expression landscape. We study the biological BCP behaviour and seek its lineage combining in vivo imaging techniques with the generation of new transgenic lines by the CRISPR/Cas9 genome edition system.

RELATED PUBLICATIONS (LAST 10 YEARS)

Kamaid, A, Molina-Villa, T, Mendoza, V, Pujades, C., Maldonado, E, Ispizua-Belmonte, JC, Lopez-Casillas, F. Betaglycan knock-down causes embryonic angiogenesis defects in zebrafish. Genesis Jul 15, 2015

Terriente, J, Pujades, C. Cell segregation in the hindbrain: do boundaries matter? Invited review. Cell Mol Life Sci, DOI: 10.1007/s00018-015-1953-8, 2015 

Zecca, A, Dyballa, S, Voltes, A, Bradley, R, Pujades, C. The order and place of neuronal differentiation establish the topography of sensory projections and the entry points within the hindbrain. J Neurosc 35(19): 7475-86, 2015 

Joya, X, Garcia-Algar, O, Vall, O, Pujades, C. Transient exposure to ethanol during zebrafish embryogenesis results in defects in neuronal differentiation: an alternative model system to study FASD. PLoS ONE 9(11): e112851, 2014

Joya, X, Garcia-Algar, O, Salat-Batlle, J, Pujades, C, Vall, O. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. Birth Defects Res A Clin Mol Teratol Aug 18, 2014

Calzolari, S, Terriente, J, Pujades, C. Cell segregation in the rhombomeric boundaries relies in physical mechanisms based in an actomyosin cable. EMBO J Apr 1;33(7):686-701, 2014

Terriente, J, Pujades, C. The use of zebrafish embryos for small molecule screening related to cancer. Dev. Dyn. 242, no. 2, pp. 97-107, 2013

Sapède, D, Dyballa, S, Pujades, C. Cell lineage analysis reveals three different progenitor pools for neurosensory elements in the otic vesicle. J Neurosc, 32(46):16424-16434, 2012
 
Jimenez-Guri, E, Pujades, C An ancient mechanism of hindbrain patterning has been conserved in vertebrate evolution. Evol Dev, 13:1, 38-46, 2011

Jimenez-Guri, E, Udina, F, Colas, JF, Sharpe, J, Padrón, L, Torres M, Pujades, C. Clonal analysis in mice underlines the importance of positional information during hindbrain segmentation. PLoS ONE 5(4): e10112, 2010

Sapède, D., Pujades, C. Hedgehog signaling governs the development of sensory epithelium and its associated innervation in the zebrafish inner ear, J Neurosc 30: 3612-3623, 2010

Aragón, F., Pujades, C. FGF signaling controls caudal hindbrain specification through Ras-ERK1/2 pathway, BMC Dev Biol, 9:61, 2009

Alsina, B., Giraldez, F. and Pujades, C. Patterning and cell fate in inner ear development. Review in Science in Hispania Special Issue, Int J Dev Biol, 53(8-10):1503-13, 2009

Vázquez-Echeverría, C., Dominguez-Frutos, E., Charnay, P., Schimmang, T., Pujades, C. Analysis of kreisler mutants reveals new roles of the hindbrain-derived signals in the establishment of the otic neurogenic domain. Dev Biol, 322(1):167-78, 2008

Schneider-Maunoury, S., Pujades, C. Hindbrain signals in otic regionalization: walk on the wild side. Review in Ear Development Special Issue, Ed. F. Giraldez and B. Fritzch Int J Dev Biol 51(6-7):495-506, 2007

Lecaudey, V., Ulloa, E., Anselme, I., Stedman, A. Schneider-Maunoury, S., Pujades, C. Role of the hindbrain in patterning the otic vesicle: a study of the zebrafish vhnf1 mutant. Dev Biol 303, 134-143, 2007

Pujades, C., Kamaid, A., Alsina, B., Giraldez, F. BMP4 regulates the development of hair-cells by modulating progenitor cell survival. Dev Biol, Apr 1;292(1):55-67, 2006

Aragón, F., Vazquez-Echeverría, C., Ulloa, E., Reber, M., Cereghini, S., Alsina, B., Giraldez, F., Pujades, C. vHnf1 regulates specification of caudal rhombomere identity in the chick hindbrain. Dev Dyn 234(3), pp. 567-76, 2005

CURRENT COLLABORATIONS

Nadine Peyrieras, Institut Alfred Fressard, Giff-sur-Yvete
Aurora Pujol, IDIBELL, BCN
Virginie Lecaudey, BIOSS University of Freiburg
Juan R Martinez-Morales, Centro Andaluz de Biología del Desarrollo, Sevilla
José Luis Gómez-Skármeta, Centro Andaluz de Biología del Desarrollo, Sevilla
George Debregeas, Institut Jean Perrin, Paris