Transcriptomics of Vertebrate Development and EvolutionThis group is part of the EMBL/CRG Research Unit in Systems Biology
- GROUP LEADER:
- Manuel Irimia
- Jon Permanyer, Jordi Fernandez-Albert
- Javier Tapial, Chris Wyatt
Our group is interested in understanding the roles that alternative splicing plays in vertebrate embryonic development, and how novel transcript variants have contributed to shape our unique development and body plan during evolution.
Alternative splicing – the differential processing of introns and exons – is the most widespread contributor to vertebrate transcriptomic diversity, impacting more than 95% of human multiexonic genes. However, although 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 and its contribution to evolution is largely unknown.
In our first months at the CRG (from June 2014), we are combining computational and experimental approaches using in vivo systems (zebrafish and mouse) to investigate the roles of transcriptomic diversification through alternative splicing in embryonic development and evolution. In particularly we are currently focusing on two far-reaching and exciting topics: (1) the impact of post-transcriptional mechanisms in early vertebrate development, and its connections with embryonic pluripotency, stem cell biology, and the evolutionary origins of the unique mammalian placenta; and (2) how the origin of a large program of a highly conserved, neural-specific transcript variants at the dawn of vertebrates shaped neuronal protein-protein interaction networks and how this contributed to the evolution of our brain.
- Functional and evolutionary impact of neural-specific alternative splicing in vertebrates.
- The roles of alternative splicing in early mammalian embryonic development.
Irimia M†, Weatheritt RJ, Ellis J, Parikshak NN, Gonatopoulos-Pournatzis T, Babor M, Quesnel-Vallières M, Tapial J, Raj B, O’Hanlon D, Barrios-Rodiles M, Sternberg MJE, Cordes SP, Roth FP, Wrana JL, Geschwind DH, Blencowe BB†
“A highly conserved program of neuronal microexons is misregulated in autistic brains.”
Cell, 159:1511-23 (2014).
Pinho R†, Garcia V, Irimia M†, Feldman M.
“Stability depends on positive autoregulation in Boolean gene regulatory networks.”
PLoS Comp. Biol., 10: e1003916 (2014).
† Corresponding authors.