Biology subjects

Escudero, L. M.

Publications and source records attributed to Escudero, L. M..

8 recordsLinked to original sources

bioRxiv2025

A Natural Programmable Metamaterial Controls 3D Curvature of Compound Eyes

The panoramic vision of the convex compound eyes, common to insects and crustaceans, relies on micrometer-scale curvature variations1. These variations create specialized visual zones adapted to specific tasks, including detecting prey, mates, or predators2,3. However, the mechanisms by which such fine-scale curvature is encoded during development remain unknown. Here we show that the developing eye of Drosophila melanogaster functions as a natural metamaterial that programs the organs precise 3D curvature. We discover a supracellular triangular mesh in the basal retina with a specific pattern of triangles sizes. Computational simulations demonstrate its role directing the small scale curvature variations of the eye. Genetic disruption of this micropattern prevents local curvature establishment. Furthermore, the presence of a homologous mesh-curvature relationship in Drosophila mauritiana indicates evolutionary conservation of this mechanism. These results reveal a novel mechanism of morphogenesis control in which the supracellular 2D patterning give rise to a biological programmable metamaterial that encodes 3D curvature with great precision4. Our in vivo finding offers a novel framework for the design of shape-programmable 3D biological surfaces with broad implications from synthetic morphogenesis to clinical applications.

developmental biology↗

bioRxiv2025

The V-ATPase/ATG16L1 axis drives membrane remodeling during epithelial morphogenesis

Epithelial tubulogenesis shapes internal organs by transforming flat epithelial sheets or unpolarized cords into hollow tubes with central lumens. A key example is the formation of the posterior neural tube during secondary neurulation, which requires precise morphogenetic events for de novo lumen formation. Although several studies have highlighted the role of autophagy in specific morphogenetic events, its involvement in epithelial organ development remains unclear. Autophagy operates via canonical and noncanonical pathways. Canonical autophagy is catabolic, requiring double-membrane autophagosomes and the full ATG protein set. Noncanonical autophagy, including the V-ATPase/ATG16L1-dependent Conjugation of ATG8 in Single Membranes (CASM), has both degradative and non-degradative roles and regulates different membrane trafficking processes. Using human neural tube organoids, spheroids, and tube micropatterns deficient in CASM or canonical autophagy, we show that CASM plays a pivotal role in epithelial tube morphogenesis. Specifically, the V-ATPase/ATG16L1 axis is essential for de novo lumen formation by regulating membrane junction remodeling and Rab11-dependent recycling pathways. These findings reveal distinct contributions of autophagy pathways in epithelial development, with potential implications for diseases linked to autophagy dysfunction.

cell biology↗

bioRxiv2024

Computational analysis of SOD1-G93A mouse muscle biomarkers for comprehensive assessment of ALS progression

AimsTo identify potential image biomarkers of neuromuscular disease by analysing morphological and network-derived features in skeletal muscle biopsies from a murine model of amyotrophic lateral sclerosis (ALS), the SOD1G93A mouse, and wild-type (WT) controls at distinct stages of disease progression. MethodsUsing the NDICIA computational framework, we quantitatively evaluated histological differences between skeletal muscle biopsies from SOD1G93A and WT mice. The process involved the selection of a subset of features revealing these differences. A subset of discriminative features was selected to characterise these differences, and their temporal dynamics were assessed across disease stages. ResultsOur findings demonstrated that muscle pathology in the mutant model evolves from early alterations in muscle fibre arrangement, detectable at the presymptomatic stage through graph theory features, to the subsequent development of the typical morphological pattern of neurogenic atrophy at more advanced disease stages. ConclusionsOur assay identifies a neurogenic signature in mutant muscle biopsies, even when the disease was phenotypically imperceptible. KEY POINTS- NDICIA analysis detected differences between SOD1G93A and WT muscles at presymptomatic stage through the analysis of graph theory features. - Our computational tool identified different neurogenic-like traits in the ALS mouse model at all analysed stages of disease progression. - Differences between SOD1G93A and WT muscle images became more pronounced as the disease advanced. - The integration of UMAP into the upgraded NDICIA framework was validated as a robust alternative to PCA. - Muscle fibre characteristics in SOD1WT closely resembled those of WT mice.

neuroscience↗

bioRxiv2024

Local and global changes in cell density induce reorganisation of 3D packing in a proliferating epithelium.

Tissue morphogenesis is intimately linked to the changes in shape and organisation of individual cells. In curved epithelia, cells can intercalate along their own apicobasal axes adopting a shape named "scutoid" that allows energy minimization in the tissue. Although several geometric and biophysical factors have been associated with this 3D reorganisation, the dynamic changes underlying scutoid formation in 3D epithelial packing remain poorly understood. Here we use live-imaging of the sea star embryo coupled with deep learning-based segmentation, to dissect the relative contributions of cell density, tissue compaction, and cell proliferation on epithelial architecture. We find that tissue compaction, which naturally occurs in the embryo, is necessary for the appearance of scutoids. Physical compression experiments identify cell density as the factor promoting scutoid formation at a global level. Finally, the comparison of the developing embryo with computational models indicates that the increase in the proportion of scutoids is directly associated with cell divisions. Our results suggest that apico-basal intercalations appearing just after mitosis may help accommodate the new cells within the tissue. We propose that proliferation in a compact epithelium induces 3D cell rearrangements during development. Summary statementThe study uses sea star embryogenesis as a model of a proliferating epithelium to highlight how cell division induces 3D cell rearrangements during development.

developmental biology↗

bioRxiv2024

BiaPy: A unified framework for versatile bioimage analysis with deep learning

BiaPy is an open-source library and application that streamlines the use of common deep learning approaches for bioimage analysis. Designed to simplify technical complexities, it offers an intuitive interface, zero-code notebooks, and Docker integration, catering to both users and developers. While focused on deep learning workflows for 2D and 3D image data, it enhances performance with multi-GPU capabilities, memory optimization, and scalability for large datasets. Although BiaPy does not encompass all aspects of bioimage analysis, such as visualization and manual annotation tools, it empowers researchers by providing a ready-to-use environment with customizable templates that facilitate sophisticated bioimage analysis workflows.

bioinformatics↗

bioRxiv2023

CartoCell, a high-throughput pipeline for accurate 3D image analysis, unveils cell morphology patterns in epithelial cysts.

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our Single-cell Cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues. MOTIVATIONA major bottleneck in developing neural networks for cell segmentation is the need for labor-intensive manual curation in order to develop a training dataset. The present work addresses this limitation by developing an automated image analysis pipeline that utilizes small datasets to generate accurate labels of cells in complex, 3D epithelial contexts. The overall goal is to provide an automatic and feasible method to achieve high-quality epithelial reconstructions and to enable high-content analysis of morphological features, which can improve our understanding of how these tissues self-organize.

developmental biology↗

bioRxiv2020

A quantitative principle to understand 3D cellular connectivity in epithelial tubes

Epithelial cell organization and the mechanical stability of tissues are closely related. In this context, it has been recently shown that packing optimization in bended/folded epithelia is achieved by a surface tension energy minimization mechanism that leads to a novel cellular shape: the scutoid. However, further cellular and tissue level implications of this new developmental paradigm remain unknown. Here we focus on the relationship between this complex cellular shape and the connectivity between cells. We address this problem using a combination of computational, experimental, and biophysical approaches in tubular epithelia. In particular, we examine how energy drivers affect the three-dimensional packing of these tissues. We challenge our biophysical model by reducing the cell adhesion in epithelial cells. As a result, we observed an increment on the cell apico-basal intercalation propensity that correlated with a decrease of the energy barrier necessary to connect with new cells. We conclude that tubular epithelia satisfy a quantitative biophysical principle, that links tissue geometry and energetics with the average cellular connectivity.

developmental biology↗

bioRxiv2017

EpiGraph: an open-source platform to quantify epithelial organization

During development, cells must coordinate their differentiation with their growth and organization to form complex multicellular structures such as tissues and organs. Healthy tissues must maintain these structures during homeostasis. Epithelia are packed ensembles of cells from which the different tissues of the organism will originate during embryogenesis. A large barrier to the analysis of the morphogenetic changes in epithelia is the lack of simple tools that enable the quantification of cell arrangements. Here we present EpiGraph, an image analysis tool that quantifies epithelial organization. Our method combines computational geometry and graph theory to measure the degree of order of any packed tissue. EpiGraph goes beyond the traditional polygon distribution analysis, capturing other organizational traits that improve the characterization of epithelia. EpiGraph can objectively compare the rearrangements of epithelial cells during development and homeostasis to quantify how the global ensemble is affected. Importantly, it has been implemented in the open-access platform FIJI. This makes EpiGraph very user friendly, with no programming skills required.

developmental biology↗