Transcriptomics of vertebrate development and evolution
- Group page
- Research lines
- Group members
- Publications at CRG
2011-2014: Postdoc in the laboratory of Prof. Blencowe, University of Toronto, Toronto, Canada.
2011-2011: Postdoc in the laboratory of Prof. Fraser, Stanford University, USA.
2006-2010: PhD in Genetics in the laboratory of Prof. Garcia-Fernandez, Universitat de Barcelona, Barcelona, Spain.
2005-2006: Postgrad researcher in the laboratory of Prof. Penny, Massey University, Parlmerston North, New Zealand.
2004-2005: Postgrad researcher in the laboratory of Prof. Arctander, University of Copenhagen, Copenhagen, Denmark.
2000-2004: Diploma studies in Genetics, Universidad Complutense de Madrid, Madrid, Spain
We are interested in understanding the roles that alternative splicing and other mechanisms of transcriptomic diversification play in vertebrate embryonic development, and how novel transcript variants have contributed to shape the unique vertebrate development and body plan during evolution.
One of the major questions in developmental biology is how the wealth of different cell types that form an adult organism are specified from a single genome sequence. Decades of research have shown that this is achieved by the dynamic generation of unique, cell-specific transcriptomes through embryonic development.
The specificity of these transcriptomes is produced by tight transcriptional regulation of gene expression, but also by a plethora of post-transcriptional mechanisms that vastly expand transcriptomic complexity. Among the latter, alternative splicing – the differential processing of introns and exons to generate multiple mRNA or non-coding RNA isoforms – is the most widespread contributor to vertebrate transcriptomic diversity, impacting more than 95% of human multiexonic genes.
While alternative splicing has been implicated in nearly all biological processes in which it has been investigated, as well as in cancer and many other pathologies, its role in vertebrate development has been largely investigated in the context of conferring cell identity and (terminal) differentiation of a few specific cell types (primarily neurons, myoblasts and immune cells). This is, at least in part, likely due to the strong focus that research on developmental biology has traditionally placed on gene-level expression studies and transcriptional control by master regulators. However, many variants produced by alternative splicing and other post-transcriptional mechanisms have been shown to modify protein function in dramatic ways, in some cases resulting in antagonistic roles.
One of the most striking examples of this is provided by microexons. These tiny exons, which can encode as little as one or two aminoacids, are switched on during neuronal differentiation and show unmatched evolutionary conservation. They are often located in structured domains of proteins, where they subtly sculpt their interaction surfaces thereby modulating protein-protein interactions. Although we are still beginning to unveil their biological functions, we already know they crucial for proper neuritogenesis, axon guidance, and neuronal function. Moreover, their misregulation in the brains of some human patients with autism spectrum disorder has opened new and unexpected venues of research to understand the molecular bases of these complex mental disorders.
These and many other examples therefore highlight that gene-level expression studies of embryonic development alone may miss important information, while an integrated multilayered view of gene regulation will best capture how transcriptome remodeling drives development and evolution. Our lab combines computational and experimental approaches using in vivo systems (zebrafish and mouse) to investigate the roles of transcriptomic diversification in embryonic development and evolution, and integrate this information with data obtained from analyzing other layers of gene regulation.
- December 2015: Yamile Márquez has been awarded an EMBO long term post-doctoral fellowship.
- November 2015: Victoria Rodriguez-Vaello has been awarded a Boehringer-Ingelheim PhD fellowship.
- October 2015: Laura Lopez-Blanch has been awarded a FPI PhD Fellowship.
- September 2015: Elisabeth Kita has been awarded an ImPuLSe post-doctoral fellowship.
- May 2015: Bárbara Pernaute has been awarded a Marie Skłodowska-Curie Individual Fellowship.
- April 2015: We have been awarded a Plan Nacional grant from MINECO, including a FPI fellowship.
- March 2015: Antonio Torres-Méndez has been awarded a FPI-SO PhD Fellowship.
- January 2015: Thomas Spruce has been awarded an ImPuLSe post-doctoral fellowship.
- December 2014: “A highly conserved program of neuronal microexons is misregulated in autistic brains” is published in Cell.
- November 2014: Manuel Irimia has been awarded a Starting Grant from the European Research Council.
- September 2014: Javier Tapial has been awarded a FPI-SO PhD Fellowship.
- March 2014: Chris Wyatt has been awarded a La Caixa PhD Fellowship.
Atlas of alternative splicing profiles across animal tissues, cell types and developmental stages.