Institute of Anatomy

Research

Developmental Biology and Regeneration

Research interest

In contrast to adult mammals, zebrafish have the capacity to regenerate their hearts upon several types of injury. In the laboratory, we use cryoinjury, to induce a cardiac tissue damage with the aim to mimic the consequences of tissue loss upon myocardial infarction González-Rosa and Mercader, 2012). Upon eliminating up to ¼ of the cardiac ventricle zebrafish are able to regenerate the damaged myocardium and recover cardiac function (González-Rosa et al., 2014). Massive collagen depositions precede the process of cardiac regeneration, revealing that, in contrast to mammals, cardiac fibrosis is reversible in the zebrafish and occurs as an intermediate step during regeneration (González-Rosa et al., 2011). We are interested in understanding the mechanisms through with in the zebrafish, the fibrotic tissue, including extracellular matrix and myofibroblast regress, as this might have implications for the design of antifibrotic strategies in mammals. We are also interested in understanding which are the cells contributing to the fibrotic response.

Rückbildung des fibrotischen Gewebes und Herzregeneration nach einer Kryolesion am Zebrafischherz — Figure 1. Fibrotic tissue regression and cardiac regeneration upon ventricular cryoinjury in the zebrafish. Immunostaining of cryoinjured hearts at different days postinjury (dpi). Cryoinjury leads to fibrotic tissue deposition (anti-MLCK, green) with gets eliminated and is no longer visible at 100 dpi. Myocardium is shown in red (anti-MHC antibody staining), nuclei at counterstained in blue. ba = bulbus arteriosus; IA = injured area; V = ventricle.

Group Developmental Biology and Regeneration

Group members

Group Mercader CNIC

News

Unbenanntes Dokument

June 2020
Welcome João and Nick, Goodbye Carolina and Andres! Scaf1 loss of function manuscript now online at EMBO Reports!
May 2020
Nadia gets awarded the Max Cloetta Prize 2020!
April 2020
Congrats to Myra for joining the COMET mentoring Program for female postdoctoral fellows.
March 2020
Nadia got promoted to Full Professor.
February 2020
Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity Rodius et al, 2020 Sci Rep.
January 2020
Kick-off of REANIMA, H2020 Project led by CNIC.
Myra Chávez joins the group as a postdoctoral fellow.
December 2019
Zoltan Varga, from ZIRC, is visiting our lab for a short sabbatical.
Celebration of 4DHeart Winter School in Bern.
November 2019
Welcome Magdalena Figlmüller, MSc Student from University of Vienna
October 2019
Posting of the results on the functional analysis of SCAF1 on bioRxiv García-Poyatos et al.
Anna Gliwa joins the group.
Our peer-reviewed version on the role of sox10-positive cardiomyocytes is out in Cell Reports.
September 2019
Second internship of Vinzenzo Di Donato.
We welcome our Masterstudent Andrej Vianin.
Review on Zebrafish as a model for organ regeneration is out.
Happy to contribute to preprint on the role of cilia proteins controlling Yap1 during heart development.
August 2019
PhD defense of Marcos Sande-Melón. Our first Swiss Doctor!
July 2019
“Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells” Congratulations to Laura and Alex and the rest of authors!.
Celebration of the joint 4DHeart and CEM Summer School
Our research article on the role of Wt1 and macrophages during heart regeneration is out at Cell Reports.
June 2019
check out our new preprint “Pre-existent adult sox10⁺ cardiomyocytes contribute to myocardial regeneration in the zebrafish”.
We enjoyed our lab retreat 2019 in Zermatt.
May 2019
Inês Marques has been accepted to the COMET Career Programme at the University of Bern and Indré Piragyté-Langa received an UniBE Initiator grant. Congrats to our postdocs!
April 2019
Congrats to Andrés Sanz-Morejón for winning a Best oral presentation award at the Swiss Zebrafish conference 2019!
March 2019
We welcome Benedetta Coppe, who start her PhD in our group.
February 2019
Happy to have contributed to “Retinal microglia signaling affects Müller cell behavior in the zebrafish following laser injury induction” published in Glia. Thanks to Federica Conedera and Volker Enzmann for the collaboration.
December 2018
Nadia Mercader received an ERC Consolidator Grant for the Project TransReg- 819717.
October 2018
Vincenzo Di Donato from Zeclinics spent a short internship in the lab and Marius Botos joined the group as a bioinformatician.
September 2018
We welcome Indré Piragyte-Langa, anew postdoctoral fellow in the group.
We got featured in the September issue of Unipress.
June 2018
We are proud to announce the publication of a Special Issue on Regeneration at the International Journal of Developmental Biology edited by Florenci Serras and Nadia Mercader.
May 2018
A preprint on our work on proepicardium formation is online.
We enjoyed our group retreat at Lac Léman.
Congratulation to Andrés, for winning the best poster prize at the 9^th Ascona International Workshop on Cardiomyocyte Biology AND the 11^th Swiss Zebrafish conference!!
April 2018
We are happy to announce that the Human Frontier Science Program has granted the project Handling OXPHOS structural heterogeneity and metabolic plasticity (starting date Summer 2018). The project is coordinated by José Antonio Enriquez (CNIC, Spain) and counts with the participation of Karin Busch (University Münster, Germany), James Eberwine (University of Pennsylvania, USA) and ourselves.
During this month, Daniel Windecker performed his Matura project on zebrafish heart regeneration in our group.
Our paper on Transient Fibrosis regression during heart regeneration in the zebrafish is now online at PNAS.
February 2018
on bioRxiv Sánchez-Iranzo et al., Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
January 2018
New Publication: Sánchez-Iranzo et al., Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
September 2017
Participating at Nacht der Forschung.
June 2017
Enjoying our group retreat !
New article: Awasthi Mishra N, Drögemüller C, Jagannathan V, Keller I, Wüthrich D, Bruggmann R, Beck J, Schütz E, Brenig B, Demmel S, Moser S, Signer-Hasler H, Pieńkowska-Schelling A, Schelling C, Sande M, Rongen R, Rieder S, Kelsh RN, Mercader N, Leeb T. A structural variant in the 5'-flanking region of the TWIST2 gene affects melanocyte development in belted cattle. PLoS One. 2017 Jun 28;12(6):e0180170
March 2017
New publication. Vazão H, Rosa S, Barata T, Costa R, Pitrez PR, Honório I, de Vries MR, Papatsenko D, Benedito R, Saris D, Khademhosseini A, Quax PH, Pereira CF, Mercader N, Fernandes H, Ferreira L. High-throughput identification of small molecules that affect human embryonic vascular development. Proc Natl Acad Sci U S A. 2017 Mar 27.
February 2017
We are happy to announce two new PhD training programs:
4D analysis of heart development and regeneration using advanced light microscopy
PhD specialization: Cutting Edge Microscopy.
January 2017
Hosting of the 10th Swiss Zebrafish Conference.
December 2016
Ronja Baal joins the Group.
November 2016
Kick off meeting liveHeart.
October 2016
Cogliati S, Calvo E, Loureiro M, Guaras AM, Nieto-Arellano R, Garcia-Poyatos C, Ezkurdia I, Mercader N, Vázquez J, Enriquez JA. Mechanism of super-assembly of respiratory complexes III and IV. Nature. 2016 Oct 24;539(7630):579-582.
September 2016
Attending the EMBO conference on The molecular and cellular basis of regeneration and tissue repair in Salerno.
August 2016
Eduardo Díaz from CNIC is visiting us.
July 2016
Fabian Häberli joins the group.
June 2016
Alexander Ernst starts his PhD within the project liveHeart.
May 2016
Neue Publikation:
Analysis of the dynamic co-expression network of heart regeneration in the zebrafish.
April 2016
Jose Antonio Enriquez and Rui Benedito from CNIC visited us
Shaira Murugan joined the lab.
March 2016
Neue Publikationen:
2C-Cas9: a versatile tool for clonal analysis of gene function.
Interplay between cardiac function and heart development.
February 2016
First Group retreat celebrated in Bern 19-21th February.
January 2016
Carolina García, Marcos Sande and Andrés Sanz join the Institute of Anatomy.
December 2015
Marcos Sande wins the best Poster Prize at YLS Salamanca 2015.
November 2015
Andrés Sanz wins the 1st prize of the Spanish National XIV Certamen Universitario ARQUIMEDES, for his Master thesis.

CNIC Konferenz 2016

Mechanical forces in physiology and disease.
Webseite - Poster

more about research

The epicardium, the outer layer covering the myocardium contains precursors contributing to the fibrotic response observed after cryoinjuring the zebrafish heart (González-Rosa et al., 2012). We are interested in analysing the mechanisms of epicardium reestablishment as well as the influence of this layer during the regeneration process.

Der Herzschlag ist wichtig für die Entwicklung des Proepikards — Figure 2. Lack of a Heartbeat impairs Proepicardium formation. 3D reconstructions (A, B) and confocal sections (C, D) of a 60 hours old zebrafish larvae of the Epi:GFP line expressing GFP in proepicardial (PE) and some pericardial cells. The myocardium is stained in red (Myosin heavy chain immunohistochemistry) and cell nuclei are counterstained with DAPI. Note that a PE cell cluster is visible in control samples but absent in larvae treated for 5 hours with 20 mM 2,3-Butane Monoxime, a drug stopping cardiac contraction. At = atrium; PE = proepicardium; V = ventricle.

We are also interested in analysing how the epicardium forms during embryonic development. The epicardium derived from the proepicardium, a cell cluster emerging at the inflow region of the forming heart tube (Peralta et al., 2014). Using live imaging in zebrafish embryos we are studying the mechanisms through which proepicardial cells are emerging from the pericardial wall and attach to the myocardium. We found that proepicardial cells detach from the pericardial wall and are advected around the cardiac ventricle, and subsequently attach to its surface (Peralta et al., 2013). We also found that this process is dependent on the heartbeat. Our current effort is dedicated to understand the underlying mechanosensory pathways as well as the role of extracellular and secreted molecules controlling proepicardium and epicardium formation.

Selected Publications

Unbenanntes Dokument

Scaf1 promotes respiratory supercomplexes and metabolic efficiency in zebrafish
García‐Poyatos C et al, 2020

Actin dynamics and the Bmp pathway drive apical extrusion of proepicardial cells.
Andrés-Delgado L, Ernst A, et al., 2019

Respiratory supercomplexes provide metabolic efficiency in zebrafish
García-Poyatos et al., 2019

Pre-existent adult sox10⁺ cardiomyocytes contribute to myocardial regeneration in the zebrafish.
Marcos Sande-Melón et al., 2019

Pre-existent adult sox10⁺ cardiomyocytes contribute to myocardial regeneration in the zebrafish.
Marcos Sande-Melón et al. Cell Reports, 2019

Model systems for regeneration: zebrafish.
Marques et al., 2019

Wilms Tumor 1b Expression Defines a Pro-regenerative Macrophage Subtype and Is Required for Organ Regeneration in the Zebrafish
Sanz-Morejón A et al., 2019

Actomyosin dynamics, Bmp and Notch signaling pathways drive apical extrusion of proepicardial cells.
Laura Andrés-Delgado, Alexander Ernst, María Galardi-Castilla, David Bazaga, Marina Peralta, Juliane Münch, Juan Manuel González-Rosa, Federico Tessadori, Jeroen Bakkers, José Luis de la Pompa, Julien Vermot, Nadia Mercader, 2018

Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
Sánchez-Iranzo et al., 2018

Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.
Sánchez-Iranzo et al., 2018

Interplay between cardiac function and heart development.
Andrés-Delgado & Mercader, 2016

Use of Echocardiography Reveals Reestablishment of Ventricular Pumping Efficiency and Partial Ventricular Wall Motion Recovery upon Ventricular Cryoinjury in the Zebrafish.
González-Rosa et al., 2014

Heartbeat-Driven Pericardiac Fluid Forces Contribute to Epicardium Morphogenesis.
Peralta et al., 2013

Cryoinjury as a myocardial infarction model for the study of cardiac regeneration in the zebrafish.
González-Rosa et al., 2012

Pan-epicardial lineage tracing reveals that epicardium derived cells give rise to myofibroblasts and perivascular cells during zebrafish heart regeneration.
González-Rosa et al., 2012

Extensive scar formation and regression during heart regeneration after cryoinjury in zebrafish.
González-Rosa et al., 2011

Unbenanntes Dokument

Further Publications

Unbenanntes Dokument

TGF-β Signaling Promotes Tissue Formation during Cardiac Valve Regeneration in Adult Zebrafish.
Bensimon-Brito et al, 2020

Diverse Signaling by TGFβ Isoforms in Response to Focal Injury is Associated with Either Retinal Regeneration or Reactive Gliosis.
Conedera FM, Quintela Pousa AM, Presby DM, Mercader N, Enzmann V, Tschopp M, 2020

Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity
Rodius S, de Klein N, Jeanty C, Sánchez-Iranzo H, Crespo I, Ibberson M,, 2020

Retinal microglia signaling affects Müller cell behavior in the zebrafish following laser injury induction.
Conedera FM, Pousa AMQ, Mercader N, Tschopp M, Enzmann V., 2019

Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart.
Lowe V, Wisniewski L, Sayers J, Evans I, Frankel P, Mercader-Huber N, Zachary IC, Pellet-Many C,, 2019

Intraflagellar transport complex B proteins regulate the Hippo effector Yap1 during cardiogenesis.
Peralta et al., 2019

Models to crack the code of organ regeneration.
Mercader N. & Serras F., 2018

Can broken hearts be mended? Ken Poss, a pioneer on heart regeneration research.
Mercader N. & Serras F., 2018

Elly Tanaka’s passion for exploring animal regeneration.
Mercader N. & Serras F., 2018

A structural variant in the 5'-flanking region of the TWIST2 gene affects melanocyte development in belted cattle.
Awashti et al., 2017

High-throughput identification of small molecules that affect human embryonic vascular development.
Vazão et al., 2017

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish.
Cogliati S. et al, , 2016

2C-Cas9: a versatile tool for clonal analysis of gene function.
Di Donato et al., 2016

Analysis of the dynamic co-expression network of heart regeneration in the zebrafish.
Rodius S. et al., 2016

Heart regeneration: dream or reality?
Mercader N. et al., 2013

Proepicardial cells go for a swim: how fluid flows guide epicardial progenitors to the heart.
Mercader N. et al., 2013

Unbenanntes Dokument

Grants

Unbenanntes Dokument

Schweizerischer Nationalfonds (SNF)

ERC Consolidator Grant 2018 TransReg

liveHeart

4DHeart

Human Frontier Science Program Project Grant RGP0016/2018-104

874764 — REANIMA — H2020-SC1-BHC-2018-2020/H2020-SC1-2019-Single-Stage-RTD

Job offers

We are seeking to recruit a Bioinformatician with expertise in transcriptomics. Please contact nadia.mercader@ana.unibe.ch for further details.

We are currently looking for enthusiastic undegraduate students interested in performing their Master in science project on cardiac development or heart regeneration in the zebrafish.

Please write an email including a motivation letter and CV to nadia.mercader@ana.unibe.ch.