Multicellular Dynamics

Molecular and cellular mechanisms regulating epithelia morphogenesis and homeostasis

Dra Maria Dolores (Lola) Martín Bermudo

Principal Investigator

Summary

1. Understanding the molecular and cellular mechanisms regulating epithelia morphogenesis and homeostasis

Our laboratory primarily focuses on 2 major research lines: (1) mechanisms underlying cell migration and invasion, and (2) contribution of cell–ECM interactions to epithelial morphogenesis and homeostasis. We employ a multidisciplinary approach integrating genetics, transcriptomics, 4D imaging, biophysics, and computational analysis.
In the context of cell migration, we have shown that, beyond its classical role as a substrate, the ECM can regulate migration by exerting mechanical constraints on the 3D environment through which cells move (Molina et al., PLoS Biol., 2023). Our group has also identified several novel regulators of Ras-driven cell invasion. These include EGRAP, a new EGFR negative regulator (Soler et al., PLoS Genetics, 2021); the Tensin family (Martínez-Abarca et al., Genes, 2023); integrins (Martínez-Abarca et al., Cancer, 2024); and ECM components, such as laminins. Recently, we uncovered key regulators of the tumor-promoting crosstalk between epithelial tumor cells and adjacent mesodermal cells, which include regulators of zinc metabolism, the Hh signaling pathway members, and vesicle trafficking.
In relation to the role of cell–ECM interactions in epithelial morphogenesis and homeostasis, we have shown that a balance between the mechanical forces generated by epithelial cells and those exerted by the ECM is essential for the cell shape changes driving organogenesis. This has been demonstrated in diverse model systems, including the egg chamber (Santa-Cruz et al., PLoS Genetics, 2020; Hernández-del Valle et al., BMC Biol., 2022), the embryonic tracheal system (Klubmann et al., Cell Reports, 2022), and the wing (Valencia-Expósito et al., Front. Cell and Dev. Biol., 2022; EMBO Journal, 2025). We have also shown that cell–ECM interactions regulate epithelial SC proliferation via modulation of Notch signaling (Rincón-Ortega et al., Front. Cell and Dev. Biol., 2023), and that the mechanical context determines integrin requirement in maintaining epithelial architecture.

I am a founder of the charity DrosAfrica, with the mission of helping to set up an African research community using Drosophila as a model system for human diseases of interest in the area (see http://drosafrica.org for details).

Publications over the last 5 years

MLAB

1. Santa-Cruz Mateos, C., Valencia-Expósito, A., Palacios, I.M. and Maria D. Martin-Bermudo (2020) Integrins regulate epithelia cell shape by controlling the architecture and mechanical properties of basal actomyosin networks. PLoS Genetics, 16 (6). https://doi.org/10.1371/journal.pgen.1008717.

2. Soler Beatty, J., Molnar, C., Luque, C.M., de Celis J.F. and Martin-Bermudo, M.D.* (2021) EGFRAP encodes a new negative regulator of the EGFR acting in both normal and oncogenic EGFR/Ras-driven tissue morphogenesis. PLoS Genetics. Aug. https://doi.org/10.1371/journal.pgen.1009738

3. Hernández-del-Valle, M., Valencia-Expósito, A., López-Izquierdo, A., Casanova-Ferrer, P., Tarazona, P., Martín-Bermudo, M. D., and Míguez Gómez, D. (2022) A coarse-grained approach to model the dynamics of the actomyosin cortex. BMCB https://doi.org/10.1186/s12915-022-01279-2

4. Klubmann-Fricke, B.J., Martín-Bermudo, M.D.* and Llimargas, M.*. (2022) The Basement Membrane controls size and integrity of the Drosophila tracheal tubes. Cell Reports, 39. https://doi.org/10.1016/j.celrep.2022.110734

5. Valencia-Expósito^,A., Gómez-Lamarca, M.J., Widmann, T. and Martín-Bermudo, M.D. (2022) Integrins cooperate with the EGFR/Ras pathway to promote epithelia survival and architecture in development and oncogenesis. Front. Cell Dev Biol., 13 June 2022. https://doi.org/10.3389/fcell.2022.892691

6. Rincón-Ortega, L., Valencia-Expósito, A., Kabanova, A., González-Reyes, A.^* and Martín-Bermudo, M.D.* (2023) Integrins control epithelial stem cell proliferation in the Drosophila ovary by modulating the Notch pathway. Front. Cell Dev Biol. https://doi.org/10.3389/fcell.2023.1114458

7. Molina López, E., Kabanova, A., Winkel, A., Franze, K., Palacios I.M. and Martín-Bermudo, M.D. (2023) Constriction forces imposed by basement membranes regulate developmental cell migration. PLoS Biology. https://doi.org/10.1371/journal.pbio.3002172

8. Martínez-Abarca Millán and Martín-Bermudo, M.D. (2023) Integrins act as suppressors of Ras-mediated oncogenesis in Drosophila models. Cancers, https://doi.org/10.3390/cancers15225432.

9. Valencia-Expósito, A., Khalilgharibi, N., Martínez-Abarca Millán, A, Mao, Y. and Martín-Bermudo, M.D. (2025) Unravelling principles initiating epithelial basal folding: cell-ECM lessening followed by an increase in basolateral contractility. The EMBO J., https://doi.org/10.1038/s44318-025-00384-6.

Outreach:

Palacios, I., Vicente-Crespo, M. and Martin-Bermudo, M.D. (2020) The humble fruit fly is helping the African science community to thrive. Nature Rev. Mol. Cell Biol. https://doi.org/10.1038/s41580-020-00283-0.

Lab members & Collaborators

MBLAB

Lab members

Principal investigator:

Dr. M.Dolores Martín Bermudo, +34 954348674 (EMBO MEMBER)

Postdoctoral FELLOWS:

Dr Cecilia Huertas Fernandez-Espartero

PHD STUDENTS:

Alejandro Arias Montecino
Mariano Brasal Prieto
Dhawia Elatoui (visiting PhD student from University of Sfax, Tunisia)

Asistentes de laboratorio:

OLD LAB MEMBERS:
Dra Ana Martinez-Abarca Millan
Dra Lourdes Rincón Ortega
Dra Carmen Santa-Cruz Mateos
Dra Ester Molina López
Dra Jennifer Soler Beatty
Dra Andrea Valencia Expósito
Dr Besaiz Jose Sánchez Sánchez
Dra Cecilia Huertas Fernandez-Espartero
Dra M. Jesus Gomez Lamarca
Dra Beatriz Estrada Martin
Dr Juan Jose Perez Moreno
Dr Jose M. Urbano Fernández
Beatriz Ibáñez Jiménez

COLLABORATORS

Prof. Nicholas Brown (Wellcome/CR-UK Institute, Cambridge, UK)
Prof. Acaimo González-Reyes (CABD, Sevilla)
Prof. Christos Delidakis (IMBB, Crete)
Dr David Gómez Miguez (UAM, Madrid)
Dra Marta Llimargas Casanova (IRB, Barcelona)
Dr Isabel Palacios (Queen Mary Univ. of London, UK)
Dra Mao Yanlan (LMB, University College London)
Dr Luis M. escudero (Departamento de Biología celular, Universidad de Sevilla).