Biology subjects

Martin-Bermudo, M. D.

Publications and source records attributed to Martin-Bermudo, M. D..

8 recordsLinked to original sources

bioRxiv2026

Integrin loss and tissue mechanics trigger progressive disruption of simple epithelial

Simple epithelia form cohesive sheets anchored to a basement membrane (BM), yet the mechanisms that preserve their monolayered architecture remain poorly understood. Here, we address this knowledge gap using the simple follicular epithelium of Drosophila as a model. Combining live imaging, quantitative image analysis, manipulation of BM mechanical properties and biophysical measurements, our results provide evidence supporting the role of integrins in orienting cell division in vivo. They also reveal two previously unrecognized integrin functions essential for epithelial integrity: promoting timely reintegration of displaced cells following non-planar divisions and modulating junctional tension. These activities underpin a stepwise model of epithelial disruption upon integrin removal. An initial ectopic layer arises from altered division orientation and delayed reintegration. Within this layer, integrin-mutant cells exhibit exacerbated defects in both processes, along with increased junctional tension, which together drive progressive epithelial disruption leading to multilayering. BM mechanical properties further modulate these processes, shaping regional susceptibility to disruption. Together, our work defines how integrin-mediated adhesion and BM mechanics maintain epithelial architecture, while revealing discrete intermediate stages of breakdown with potential relevance to epithelial disorganisation in diseases such as cancer.

cell biology↗

bioRxiv2025

Mechanical context defines integrin requirement for maintaining epithelia architecture

Epithelial tissues form cohesive sheets of cells anchored to an underlying basement membrane (BM). They are broadly classified as simple or stratified, each fulfilling distinct physiological roles. While mechanisms driving stratification are increasingly well characterized, those safeguarding simple epithelial architecture remain poorly defined. Here, we address this knowledge gap using the simple follicular epithelium of Drosophila as a model. Combining live imaging, quantitative image analysis, manipulation of BM mechanical properties and biophysical measurements, we uncover previously unrecognized integrin-dependent mechanisms esential for preserving simple epithelial integrity. In addition to their known role in orienting cell division, integrins regulate cell reintegration dynamics and modulate surface tension at the cellular level. We further demonstrate that the maintenance of epithelial architecture is governed by mechanisms acting across both cellular and tissue scales. In our model, BM mechanical properties--including stiffness anisotropy--cooperate with integrin-mediated adhesion and tissue geometry to preserve epithelial organization. Given the central role of epithelial disorganization in tumorigenesis, elucidating these mechanical and molecular regulators is critical for understanding epithelial morphogenesis, maintaining tissue homeostasis, and uncovering the early events of cancer progression.

cell biology↗

bioRxiv2024

Local weakening of cell-ECM adhesion triggers basal tissue folding via changes in cell shape, actomyosin organization and E-cad levels

During development, epithelial sheets sculpt organs by folding, either apically or basally, into complex 3D structures. Given the presence of actomyosin networks and cell adhesion sites on both sides of cells, a common machinery mediating apical and basal epithelial tissue folding has been proposed. However, little is known about the mechanisms regulating epithelial folding towards the basal side. Here, using the Drosophila wing imaginal disc and a multidisciplinary approach, combining genetic perturbations and computational modelling, we demonstrate opposing roles for cell-cell and cell-ECM adhesion systems during epithelial folding. Thus, while cadherin-mediated adhesion, linked to actomyosin network, regulates apical folding, a reduction on integrin-dependent adhesion, followed by changes in cell shape, organization of the basal actomyosin cytoskeleton and E-Cad levels, is necessary and sufficient to trigger basal folding. These results suggest that modulation of the cell mechanical landscape through the crosstalk between integrins and cadherins is essential for correct epithelial folding.

developmental biology↗

bioRxiv2022

Constriction forces imposed by basement membranes regulate developmental cell migration

The basement membrane (BM) is a specialized extracellular matrix, which underlies or encase developing tissues. Mechanical properties of encasing BMs have been shown to profoundly influence the shaping of associated tissues. Here, we use the migration of the border cells (BCs) of the Drosophila egg chamber to unravel a new role of encasing BMs in developmental cell migration. BCs move between a group of cells, the nurse cells (NCs), that are enclosed by a monolayer of follicle cells (FCs), enveloped in turn by a BM, the follicle BM. We show that increasing or reducing the stiffness of the follicle BM, by altering laminins or Coll IV levels, conversely affects BC migration speed and alters migration mode and dynamics. Follicle BM stiffness also controls pairwise NC and FC cortical tension. We propose that constriction forces imposed by the follicle BM influence NC and FC cortical tension, which, in turn, regulate BC migration. Encasing BMs emerge as key players in the regulation of collective cell migration during morphogenesis.

cell biology↗

bioRxiv2021

A coarse-grained approach to model the dynamics of the actomyosin cortex

The dynamics of the actomyosin machinery is at the core of many important biological processes. Several relevant cellular responses such as the rhythmic compression of the cell cortex are governed, at a mesoscopic level, by the nonlinear interaction between actin monomers, actin crosslinkers and myosin motors. Coarse grained models are an optimal tool to study actomyosin systems, since they can include processes that occur at long time and space scales, while maintaining the most relevant features of the molecular interactions. Here, we present a coarse grained model of a two-dimensional actomyosin cortex, adjacent to a three-dimensional cytoplasm. Our simplified model incorporates only well characterized interactions between actin monomers, actin crosslinkers and myosin, and it is able to reproduce many of the most important aspects of actin filament and actomyosin network formation, such as dynamics of polymerization and depolymerization, treadmilling, network formation and the autonomous oscillatory dynamics of actomyosin. Furthermore, the model can be used to predict the in vivo response of actomyosin networks to changes in key parameters of the system, such as alterations in the anchor of actin filaments to the cell cortex.

biophysics↗

bioRxiv2019

Integrins control tissue morphogenesis and homeostasis by sustaining the different types of intracellular actin networks

Forces generated by the actomyosin cytoskeleton are key contributors to the generation of tissue shape. Within the cell, the actomyosin cytoskeleton organizes in different types of networks, each of them performing distinct roles. In addition, although they normally localize to precise regions of the cells, they are rarely independent and often their dynamics influence each other. In fact, the reorganization of a given structure can promote the formation of another, conversions that govern many morphogenetic processes. In addition, maintenance of a specific actomyosin network organization in a differentiated tissue might be equally important. Failure to do so could lead to undesired cell state transitions, which in turn would have drastic consequences on the homeostasis of the tissue. Still, little is known about the mechanisms that ensure controlled transitions between actomyosin networks during morphogenesis or their maintenance in a differentiated tissue. Here, we use the Drosophila follicular epithelium to show that cell-ECM interactions mediated by integrins are necessary for the establishment and maintenance of the different actomyosin networks present in these epithelial cells. Elimination of integrins in a group of follicle cells results in changes in the F-actin levels and physical properties of their intracellular actomyosin networks. Integrin mutant follicle cells have reduced number of basal stress fibers. They also show increased cortical F-actin levels and tension, which interferes with proper basal surface growth. Finally, clonal elimination of integrins also triggers non-autonomous behavioural changes in neighbouring wild types cells, which now reorganize their actin cytoskeleton and spread and overlay the mutant ones. Based on these results, we propose that cell-ECM interactions mediated by integrins regulate epithelia morphogenesis and homesostasis by preserving the different types of intracellular actin networks.

cell biology↗

bioRxiv2018

Analysis of the role of Nidogen/entactin in basement membrane assembly and morphogenesis in Drosophila

Basement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, differentiation and maintenance. The major constituents of BMs are two independent networks of Laminin and Type IV Collagen interlinked by the proteoglycan Perlecan and the glycoprotein Nidogen/entactin (Ndg). The ability of Ndg to bind in vitro Collagen IV and Laminin, both with key functions during embryogenesis, anticipated an essential role for Ndg on morphogenesis linking the Laminin and Collagen IV networks. This was supported by results from in vitro and cultured embryonic tissues experiments. However, the fact that elimination of Ndg in C. elegans and mice did not affect survival, strongly questioned this proposed linking role. Here, we have isolated mutations in the only Ndg gene present in Drosophila. We find that while, similar to C.elegans and mice, Ndg is not essential for overall organogenesis or viability, it is required for appropriate fertility. We also find, alike in mice, tissue-specific requirements of Ndg for proper assembly and maintenance of certain BMs, namely those of the adipose tissue and flight muscles. In addition, we have performed a thorough functional analysis of the different Ndg domains in vivo. Our results support an essential requirement of the G3 domain for Ndg function and unravel a new key role for the Rod domain in regulating Ndg incorporation into BMs. Furthermore, uncoupling of the Laminin and Collagen IV networks is clearly observed in the larval adipose tissue in the absence of Ndg, indeed supporting a linking role. In light of our findings, we propose that BM assembly and/or maintenance is tissue-specific, which could explain the diverse requirements of a ubiquitous conserved BM component like Nidogen.\n\nAuthor SummaryBasement membranes (BMs) are thin layers of specialized extracellular matrices present in every tissue of the human body. Its main constituents are two networks of Laminin and Type IV Collagen linked by Nidogen (Ndg) and proteoglycans. They form an organized scaffold that regulates organ morphogenesis and function. Mutations affecting BM components are associated with organ dysfunction and several congenital diseases. Thus, a better comprehension of BM assembly and maintenance will not only help to learn more about organogenesis but also to a better understanding and, hopefully, treatment of these diseases. Here, we have used Drosophila to analyse the role of Ndg in BM formation in vivo. Elimination of Ndg in worms and mice does not affect survival, strongly questioning its proposed linking role, derived from in vitro experiments. Here, we show that in the fly Ndg is dispensable for BM assembly and preservation in many tissues, but absolutely required in others. Furthermore, our functional study of the different Ndg domains challenges the significance of some interactions between BM components derived from in vitro experiments, while confirming others, and reveals a new key requirement for the Rod domain in Ndg function and incorporation into BMs.

developmental biology↗

bioRxiv2017

Proteolytic control of centrosome activity by APC/C-Polo maintains oocyte fate in Drosophila

A universal feature of metazoan reproduction is the elimination of the maternal centrosomes prior to the end of oogenesis. In animals that have a syncytial cyst stage of oocyte development, including Drosophila and mouse, the germline centrosomes undergo a migration to all reside within the oocyte. However, the functional significance of centrosome transport within the female germline and the mechanism orchestrating this event are still a mystery. The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit ubiquitin ligase (E3) that temporally regulates progression of the cell cycle as well as the centrosome cycle. By altering the negative regulation of the cooperating ubiquitin conjugating enzyme (E2), Vihar/Ube2c, we show that temporal control of APC/C activity ensures centrosome stability and migration during early Drosophila oogenesis. When there is perduring APC/C activity, Polo kinase is precociously targeted for destruction, which results in centriole instability and decreased centrosome transport to the oocyte. We show that decreased centrosome transport correlates with a decreased accumulation of pericentriolar material (PCM) proteins on the oocyte nucleus, which results in a weakening of the structural integrity of the egg chamber and loss of oocyte fate - the overall consequence being a reduction in female fertility. Considering the conserved roles of the APC/C and Polo kinase throughout the animal kingdom and the fact that many animals have a syncytial stage of egg development, our results provide insight into the general necessity of gametic centrosome transport for female fertility.

developmental biology↗