Genome Dynamics

Control of epithelial morphogenesis in vertebrates

Dr Juan Ramón Martínez Morales

 Principal Investigator

Summary

The main focus of our laboratory is to study cellular and molecular mechanisms involved in the morphogenesis of the vertebrate eye. Using zebrafish (Danio rerio) and medaka (Oryzias latipes) as genetic models, we aim to understand this process at very different and complementary levels. We explore how gene regulatory networks control tissue identity; how this translates in precise shape changes, as well as polarized contractility and cellular adhesion; and how cellular tensions are transmitted within the tissue to determine the final shape of the organ.

 

The use of two far related teleost models (i.e. their lineages separated 200 mya) allows investigating the universality and relative contribution of the cellular and genetic mechanisms that control organ shape. In addition, due to the strategic position of teleost fish within the vertebrate evolutionary tree, our research often uncovers interesting evo-devo questions that are relevant to understand the evolutionary history of the vertebrate lineage. Therefore, questions such as, how new developmental mechanisms appear and how do they contribute to the emergence of vertebrate anatomical innovations, are among the research interests of the laboratory.

During the last years, we have become increasingly aware that an important part of our developmental studies –particularly those exploring the divergence between the neural retina and retinal pigmented epithelium (RPE) genetic programs– are also relevant in the context of retinal diseases. This seems particularly the case for retinal degenerative pathologies, for which understanding the genetic program specifying the RPE is key to improve the efficiency of recently developed cell-based therapies.

Relevant publications

Relevant publications (2012-2023)

  • Letelier J*(CA)#, Buono L*, Almuedo-Castillo M, Zang J, Mounieres C, González-Díaz S, Polvillo R, Sanabria-Reinoso E, Corbacho J, Sousa-Ortega A, Diez del Corral R, Neuhauss SCF, Martínez-Morales JR (CA)#. (2023) Mutation of Vsx genes in zebrafish highlights the robustness of the retinal specification network. Elife May 25;12:e85594. doi: 10.7554/eLife.85594.
  • Sousa-Ortega A*, Vázquez-Marín J*, Sanabria-Reinoso E, Corbacho J, Polvillo R, Campoy-López, A, Buono L, Loosli F, Almuedo-Castillo M (CA)#, Martínez-Morales JR (CA)#. (2023). A Yap-dependent mechano-regulatory program sustains cell migration for embryo axis assembly. Nat Comm. May 16th 14(1):2804.1. doi: 10.1038/s41467-023-38482-w.
  • Corbacho J, Sanabria-Reinoso E, Buono L, Fernández-Miñan A, Martínez-Morales JR (CA). (2022) Trap-TRAP, a Versatile Tool for Tissue-Specific Translatomics in Zebrafish. Front Cell Dev Biol. May 16th 14(1):2804.1. doi: 10.3389/fcell.2021.817191
  • Buono L, Corbacho J, Naranjo S, Almuedo-Castillo M, Moreno-Marmol T, de la Cerda B, Sanabria-Reinoso E, Polvillo R, Díaz-Corrales FJ, Bogdanovic O, Bovolenta P, Martínez-Morales JR. (2021) Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish. Nat Comm. Jul 27;12(1):4665.
    doi: 10.1038/s41467-021-24834-x.
  • Vázquez-Marín J, Gutiérrez-Triana JA, Almuedo-Castillo M, Buono L, Gómez-Skarmeta JL, Mateo JL, Wittbrodt J, Martínez-Morales JR. (2019). yap1b, a divergent Yap/Taz family member, cooperates with yap1 in survival and morphogenesis via common transcriptional targets. Development. Jun 21;146(13):dev173286.
    doi: 10.1242/dev.173286.
  • Letelier J#, de la Calle-Mustienes E#, Pieretti J, Naranjo S, Maeso I, Nakamura T, Pascual-Anaya J, Shubin NH*, Schneider I*, Martinez-Morales JR*, Gómez-Skarmeta JL*. (2018)  A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins. Nature Genetics 50(4):504-509.
    doi: 10.1038/s41588-018-0080-5.
  • Letelier J#, Terriente J#, Belzunce I, Voltes A, Undurraga CA, Polvillo R, Devos L, Tena JJ, Maeso I, Retaux S, Gomez-Skarmeta JL, Martínez-Morales JR*, Pujades C* (2018) Evolutionary emergence of the rac3b/rfng/sgca regulatory cluster refined mechanisms for hindbrain boundaries formation. PNAS 115(16):E3731-E3740.
    doi: 10.1073/pnas.1719885115.
  • Nicolás-Pérez M, Kuchling F, Letelier J, Polvillo R, Wittbrodt J, Martínez-Morales JR.(2016) Analysis of cellular behavior and cytoskeletal dynamics reveal a constriction mechanism driving optic cup morphogenesis. eLife. 2016 Oct 31;5. pii: e15797.
    doi: 10.7554/eLife.1
  • Gago-Rodrigues I, Fernández-Miñán A, Letelier J, Naranjo S, Tena JJ, Gómez-Skarmeta JL, Martinez-Morales JR (2015) Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis. Nat Comm  6:7054.
    doi: 10.1038/ncomms8054.
  • Tena JJ#, González-Aguilera C#, Fernández-Miñán A, Vázquez-Marín J, Parra-Acero H, Cross JW, Rigby PW, Carvajal JJ, Wittbrodt J, Gómez-Skarmeta JL*, Martínez-Morales JR* (2014) Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period. Genome Research. 24(7): 1075-85
  • Muller C#, Maeso I#, Wittbrodt J*, Martínez-Morales JR* (2013) The medaka mutation tintachina sheds light on the evolution of V-Atpase B subunits in vertebrates. Scientific Reports 3. 3217
  • Bogdanovic O#, Delfino-Machín M#, Nicolás-Pérez M, Gavilán MP, Gago-Rodrigues I, Fernández-Miñán A, Lillo C, Ríos RM, Wittbrodt J, Martínez-Morales JR# (2012) Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosis. Developmental Cell. 23 (4)

*Co-corresponding authors. #equal contribution.

Full list of publications here

Lab members & Collaborators

 

Lab members

Principal Investigator

Juan Ramón Martínez-Morales, +34 954977827, jrmarmor@upo.es

Postdoctoral

Jorge Corbacho Sanchez, +34 954978065, jcorsan1@upo.es
Ludovica Ciampi, +34 954978065, ludovicaciampi@gmail.com

PhD student

Cielo Centola Buttigliero (PID2023) +34 954978065, clcenbut@upo.es
Jesús Crespo Cuadrado (JA), +34 954978065, jcrecua@upo.es
Sofía Manzo (ProgRet-ITN) +34 954978065, sman2@upo.es

Research assistant

Rocío Polvillo Hernández, +34 954978065, rpolher@upo.es

Master Students

Andrea Del Valle Zapata +34 954978065

Visitors

 

Colaboradores

Dr Juan Tena (CABD, Seville, Spain)
Dr Miguel Moreno Mateos (CABD, Seville, Spain)
Dr Ozren Bogdanovic  (CABD, Seville, Spain)
Dr Felix Loosli (ITG, Karlsruhe, Germany)
Dr Jochen Wittbrodt (COS, Heidelberg University, Germany)
Dr Lázaro Centanin (COS, Heidelberg University, Germany)
Dra Rosa Ríos (CABIMER, Sevilla, Spain)
Dr Jerome Solon (Biofisika, Bilbao, Spain)
Dr Miguel Allende (Universidad de Chile, Chile)
Dra Paola Bovolenta (CBMSO, Madrid)
Dra Elisa Marti (IBMB, Barcelona)
Dra Cristina Pujades (UPF, Barcelona)
Dra Esther Serrano (CBMSO, Madrid)
Dr Manu Irimia (CRG, Barcelona)
Dr Joaquin Letelier (U Mayor, Chile)
Dr Stephan Neuhauss (U. Zurich)
Dra Elfride de Baere (Ghent University, Belgium)
Dr Díaz-Corrales (CABIMER, Sevilla, Spain)
Dr Sandro Banfi (TIGEM, Italy)

 

Former members

Ozren Bogdanovic (CABD, Seville)
Mariana Delfino Machin (MRC, UK)
Cristina Gonzalez Aguilera (CABIMER, Seville)
Ines Gago Rodrigues (University of Faro, Portugal)
María Nicolás Pérez (Tgen, Arizona, USA)
Silvia Naranjo Durán (CABD, Seville)
Cristian Undurraga (Chile)
Joaquin Letelier (U. Mayor, Chile)
Javier Vázquez Marín (COS-Heidelberg)
Lorena Buono (SZN, Naples)
Ana Sousa Ortega (Evidenze, Madrid)
Maria Almuedo Castillo (CABD, Seville)
Javier Macho Rendon (Cabimer, Seville)