WT1 in Cell Plasticity
Department of Cell Biology
Faculty of Biology
Physiology and Immunology
Dr. Ofelia M. Martínez Estrada
Av. Diagonal 643
08028 Barcelona, Spain
Principal investigator: Dr. Ofelia M. Martínez Estrada Postdoctoral Researcher: Dr. Ana García Melero PhD students: Marina Ramiro Pareta • Alejo Torres Cano
The Wilms’ tumor-1 (WT1) gene encodes a zinc finger protein that plays key roles during the formation of mesodermal derived tissues during embryonic development. Interestingly, latest findings indicate that WT1 is also involved in the maintenance of several adult tissues involving cells of mesodermal origin. In both scenarios increased expression of WT1 correlates with the highest plasticity state of the mesodermal progenitor cells.
We are interested in identifying the molecular mechanisms by which WT1 regulates cell plasticity, and how these influence organ formation and regeneration with especial interest in heart development and repair. We use the power of several Wt1 reporter mice and Wt1KO mice combined with the latest molecular and cellular biology tools to address the importance of WT1 in cell plasticity.
Although our research is included in basic science, our results will define the relevance of new pathways involved in cell plasticity and may impact directly in the design of new therapies or strategies for the treatment of cardiovascular disease following ischaemic damage.
Current research lines
Metabolic regulation of epicardium cell plasticity during heart development and repair
Control of epicardium cell shape and plasticity during heart formation and repair
Identification of novel pathways involved in epicardium formation
Our current projects are funded by La Caixa foundation, Health Research 2017; Spanish Society of Cardiology 2017; La Marató TV3 foundation, Heart diseases 2014; Ministry of Science, Innovation and Universities BFU2015-618135-P
Velecela V, Lettice LA, Chau YY, Slight J, Berry RL, Thornburn A, Gunst QD, van den Hoff M, Reina M, Martinez FO, Hastie ND, Martinez-Estrada OM. Wt1 regulates the expression of inhibitory chemokines during heart development. Human molecular genetics. 2013;22:5083-5095
Guadix JA, Ruiz-Villalba A, Lettice L, Velecela V, Munoz-Chapuli R, Hastie ND, Perez-Pomares JM, Martinez-Estrada OM. Wt1 controls retinoic acid signalling in embryonic epicardium through transcriptional activation of raldh2. Development. 2011;138:1093-1097
Martinez-Estrada OM, Lettice LA, Essafi A, Guadix JA, Slight J, Velecela V, Hall E, Reichmann J, Devenney PS, Hohenstein P, Hosen N, Hill RE, Munoz-Chapuli R, Hastie ND. Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of snail and e-cadherin. Nature genetics. 2010;42:89-93
Chau YY, Bandiera R, Serrels A, Martinez-Estrada OM, Qing W, Lee M, Slight J, Thornburn A, Berry R, McHaffie S, Stimson RH, Walker BR, Chapuli RM, Schedl A, Hastie N. Visceral and subcutaneous fat have different origins and evidence supports a mesothelial source. Nature cell biology. 2014;16:367-375
Segarra-Mondejar M, Casellas-Diaz S, Ramiro-Pareta M, Muller-Sanchez C, Martorell-Riera A, Hermelo I, Reina M, Aragones J, Martinez-Estrada OM, Soriano FX. Synaptic activity-induced glycolysis facilitates membrane lipid provision and neurite outgrowth. The EMBO journal. 2018;37