Remembering José Luis Gómez-Skarmeta

By Miguel L. Allende, Shawn M. Burgess, Miguel A. Moreno-Mateos, Juan-Ramon Martinez-Morales, and Ferenc Mueller

In one of the most difficult years most of us have experienced in our lifetime, we now must add mourning the loss of our colleague and friend José Luis Gómez-Skarmeta. José Luis died after a short but difficult fight with cancer. Those who knew him or his work understand what a significant loss this is to the fields of Developmental Biology, Evolution, and Genomics. José Luis was not merely a scientist but an irrepressible force of nature that pulled in everyone around him. We hope this tribute will both help his friends remember him fondly and introduce his legacy to those not lucky enough to have met him in person.

José Luis was born and raised in Santiago Chile. He moved to Spain and began his early studies in the lab of Juan Modolell on achaete and scute patterning in the drosophila imaginal disks. His early work on cis-regulation of ach and scu and later the vertebrate iroquois loci were the first hints of where his scientific interests would ultimately lead: understanding cis-regulatory elements through the lens of Developmental Biology. Over his 30 years of research, José Luis covered a wide variety of topics, but his attention kept returning to the enhancers necessary to control complex gene expression patterns and the alterations that occur in the genome to make such regulation possible. He would adapt his research to use whatever species would answer his questions and his work ultimately involved Drosophila, Xenopus, zebrafish, mice, and even Amphioxus. His work had a huge influence on our understanding of the effects of very distant enhancers, gene deserts, and the evolutionary consequences of gene regulatory blocks.

I (M.A.) had the opportunity to be a close colleague of Jose Luis´ when we both arrived at the University of Chile in Santiago in late 1997 to take up positions at the Department of Biology. He was fresh out of his PhD with Modolell and wanted to try research with vertebrates tackling the same questions he had addressed successfully with Drosophila: the establishment of genetic prepatterns in the nervous system. He was also curious to find out if he could start his independent career in his native Chile. Together with Roberto Mayor, he began working with Xenopus laevis where they investigated the function of the frog Iroquois genes using gain- and loss-of-function approaches publishing a series of very nice papers with their findings [1, 2]. During his time in Santiago, we became friends and José Luis began to ask about the virtues of the model organism I worked with, the zebrafish. I can't say I had anything to do with his later decision to move to the fish (Tom Becker may have played a more important role in that) but, after he decided to return to Spain we continued to collaborate and we published some of his first papers with the model [3-5]. Together, we embarked on work to dissect the regulatory landscape of the Iroquois clusters. José Luis had the idea to simply bioinformatically select conserved sequences in the intergenic regions of the cluster and then test them for potential enhancer activity in reporter expression assays in zebrafish and in Xenopus. We split up the work (it was a lot of injections) between Sevilla and Santiago and we generated a comprehensive dataset of regulatory sequences that fine tune the expression of these important genes. He then moved on to explore the genomic architecture of the Iroquois clusters using chromatin conformation techniques and, from there, to genome-wide analyses.

Jose Luis arrived in Seville in 2003 and became one of the founders of the Andalusian Center for Developmental Biology (CABD), a joint center between the University Pablo de Olavide and the Spanish Council of Scientific Research (CSIC). The first years were complicated since he essentially had to build everything from scratch including the aquatic vertebrate facility. It is a testament to his character and abilities that this effort was successful despite being a junior PI at CABD. After these first years Jose Luis’ lab science at CABD started to make fundamental contributions to the field of Developmental Biology through his studies using genomic and epigenetic approaches. He implemented and optimized techniques such as 4C-Seq, ATAC-Seq, ChIP-Seq, HiChIP-Seq or HiC-Seq in vivo using zebrafish, but also in other systems such as Xenopus, Medaka, Amphioxus and most recently, cavefish. Indeed, Jose Luis’ lab produced pioneering studies to understand how not only cis-regulatory elements, but also the 3D architecture of the genome, control vertebrate development [6-10]. In addition, his passion for comparative and evolutionary biology was a constant in his scientific life and by co-leading multiple collaborative projects, he was able to make seminal contributions in this field from the evolution of the appendages in vertebrates [11], to comprehensive studies on the chordate to vertebrate transition [12, 13]. Finally, it is noteworthy that from basic EvoDevo studies he was able to also contribute to a better understanding of human diseases [14, 15]. But beyond his remarkable scientific contributions and the international impact of his science, Jose Luis was the leader that all research institutes would like to have…and the truth is that CABD was Jose Luis and Jose Luis will always be CABD. He, as we mentioned above, was one of the CABD founders but more importantly he trained a pool of young scientists who are now postdocs or PIs in outstanding institutions all over the world. We are here referring to, of course, students and postdocs from his lab but also other young scientists that never were part of his team yet found in Jose Luis an amazing scientific and personal supporter of their careers, a mentor to rely on, one who never gave up… a generous person to the end as it has been mentioned many times these last weeks. He always was there for everyone, including his collaborators from 4 continents (America, Australia, Asia and Europe). He lastly had the goal to renew the CABD with new young PIs to maintain the scientific level that he, together with his colleagues at the institute, had established. He was the kind of person that being around him made you a better scientist. We have lost a fantastic and generous person, an incredibly great colleague and an outstanding mentor but it is now our duty to maintain his scientific legacy at the level he would always have wanted. Thanks Jose!

But our loss goes beyond his contributions as a scientist and a mentor. José Luis was simply a joyous person to be around. You could always hear his voice from across the room, even when that room was crowded, because he would be having an animated discussion on his most recent science or the status of Copa América cup. Like all of us, he could be angry or disappointed, but he always rebounded quickly, returning to his usual happy self in no time. He was the kind of person that would immediately invite you into his circle and treat you like you had been intimate friends forever. The world is a little sadder and a little less friendly without him in it.

1. Gomez-Skarmeta, J.L., et al., Xiro, a Xenopus homolog of the Drosophila Iroquois complex genes, controls development at the neural plate. EMBO J, 1998. 17(1): p. 181-90.

2. Glavic, A., J.L. Gomez-Skarmeta, and R. Mayor, The homeoprotein Xiro1 is required for midbrain-hindbrain boundary formation. Development, 2002. 129(7): p. 1609-21.

3. Feijoo, C.G., et al., Formation of posterior cranial placode derivatives requires the Iroquois transcription factor irx4a. Mol Cell Neurosci, 2009. 40(3): p. 328-37.

4. de la Calle-Mustienes, E., et al., A functional survey of the enhancer activity of conserved non-coding sequences from vertebrate Iroquois cluster gene deserts. Genome Res, 2005. 15(8): p. 1061-72.

5. Allende, M.L., et al., Cracking the genome's second code: enhancer detection by combined phylogenetic footprinting and transgenic fish and frog embryos. Methods, 2006. 39(3): p. 212-9.

6. Bogdanovic, O., et al., Dynamics of enhancer chromatin signatures mark the transition from pluripotency to cell specification during embryogenesis. Genome Res, 2012. 22(10): p. 2043-53.

7. Bogdanovic, O., et al., Active DNA demethylation at enhancers during the vertebrate phylotypic period. Nat Genet, 2016. 48(4): p. 417-26.

8. Gomez-Marin, C., et al., Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders. Proc Natl Acad Sci U S A, 2015. 112(24): p. 7542-7.

9. Tena, J.J., et al., An evolutionarily conserved three-dimensional structure in the vertebrate Irx clusters facilitates enhancer sharing and coregulation. Nat Commun, 2011. 2: p. 310.

10. Tena, J.J., et al., Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period. Genome Res, 2014. 24(7): p. 1075-85.

11. Letelier, J., et al., A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins. Nat Genet, 2018. 50(4): p. 504-509.

12. Acemel, R.D., et al., A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation. Nat Genet, 2016. 48(3): p. 336-41.

13. Marletaz, F., et al., Amphioxus functional genomics and the origins of vertebrate gene regulation. Nature, 2018. 564(7734): p. 64-70.

14. Martin, D., et al., Genome-wide CTCF distribution in vertebrates defines equivalent sites that aid the identification of disease-associated genes. Nat Struct Mol Biol, 2011. 18(6): p. 708-14.

15. Smemo, S., et al., Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature, 2014. 507(7492): p. 371-5.

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