Biology subjects

Alpar, L.

Publications and source records attributed to Alpar, L..

5 recordsLinked to original sources

bioRxiv2026

Tissue mechanics sets developmental scaling of collective cell migration

Despite substantial variation in adult size, animals within a species maintain consistent tissue patterns and shapes, a core property known as developmental scaling or size invariance. Developmental scaling has predominantly been attributed to the scaling of morphogen gradients and gene patterns to maintain positional information and cell fate specification1,2. However, development also necessitates collective cell flows that reshape tissues and reposition cells3,4. How these flows adapt to body size remains unclear. By combining quantitative live imaging, experimental perturbations, and physical modeling in the Drosophila thorax epithelium, we address this question in the context of a fundamental process: collective cell migration. We find that migration velocity scales linearly with tissue size, accounting for size-invariant cell positioning. While gene patterning scales with tissue size and modulates force generation, it is not sufficient to ensure proper velocity scaling. Instead, tissue mechanical properties govern the dependence of migration velocity on tissue size, enabling developmental scaling within the physiological range of animal sizes. These findings uncover principles and limits of size invariance by revealing how tissue mechanics sets the scaling behavior of collective cell flows with organismal size.

developmental biology↗

bioRxiv2026

Morphodynamic domains enable integration of live morphometrics and spatial transcriptomics

Tissue development emerges from the coordinated behaviors of thousands of cells, orchestrated by gene regulatory networks. Recent methodological advances now enable high-resolution live imaging of cell- and tissue-scale dynamics and the construction of spatially resolved gene expression atlases. However, quantitatively linking these modalities remains a central challenge, limiting our ability to understand how gene regulatory networks drive cell- and tissue-scale behaviors. Here, using the Drosophila thorax epithelium as a model system, we introduce an analytical and computational framework based on tissue morphodynamic domains: regions defined by coherent cell and tissue dynamics extracted from live imaging morphometrics. Integrating morphodynamic domains with spatial transcriptomics enables the inference of gene regulatory networks associated with distinct spatial cell- and tissue-level behaviors. Statistical cross-scale analyses further allow the interrogation and validation of gene function, confirming or revealing regulators of specific morphogenetic dynamics. In particular, our framework uncovers a role for the Toll-like receptor Tollo in modulating tissue flow, contraction, and apoptosis. Together, our work establishes a framework that integrates spatial transcriptomics with quantitative, multiscale live morphometrics, providing a generalizable strategy to probe and understand developmental processes.

developmental biology↗

bioRxiv2025

Toll receptors mediate tissue intrinsic surveillance against aberrant cells by detecting cell fate aberrations

Tissue-intrinsic surveillance systems play an important role in maintaining tissue health by detecting and eliminating aberrant cells. One such system, interface surveillance, is activated by differences in cell fate programs between neighboring cells. Activation of interface surveillance drives separation and elimination of aberrant cells by recruitment of actin regulators and Myosin II to neighboring cell contacts, as well as activation of JNK signaling and apoptosis in cells at this interface. Here, we uncover the role of long Toll receptors (Toll-2, Toll-6, Toll-7, Toll-8) as key mediators of interface surveillance in Drosophila wing imaginal discs. Using genetic mosaics combined with spatial mapping of Toll receptor expression patterns, we demonstrate that differences in long Toll receptor expression levels between neighboring cells trigger all hallmark responses of interface surveillance. This response is position-dependent and relies on the comparison of expression levels established by cell-fate-specifying programs. Specifically, we show that the expression of long Toll receptors is regulated by multiple fate-patterning pathways, giving rise to a combinatorial cell surface code that is deregulated in developmentally aberrant or oncogenic cells. Remarkably, Toll receptor-mediated surveillance operates independently of canonical NF-{kappa}B signaling, and rather mirrors a distinct role of long Toll receptors in modulating cell-cell affinity via actomyosin dynamics during early embryogenesis. Our findings identify long Toll receptors as integrators of developmental patterning and tissue homeostasis mechanisms and provide insights into how tissues detect and respond to potentially oncogenic mutations that misregulate cell fate specification pathways.

cell biology↗

bioRxiv2025

Drosophila Toll-2 controls homeotic domain formation and timing of folding

Tissue compartmentalization is a fundamental feature of animal development, crucial for determining cell fate, growth, and organ morphogenesis. Hox genes play essential and conserved roles in specifying homeotic compartments along the antero-posterior axis of the body. Despite extensive characterization of homeotic gene regulation, the mechanisms underlying the formation, maintenance, and reshaping of homeotic compartments during development remain incompletely understood. Here, we investigate the role of the Toll-2 receptor in the formation and folding of the Deformed (Dfd) homeotic compartment, which produces the neck of adult Drosophila. We show that Toll-2 is essential for properly forming the bilateral Dfd compartment through the fusion of the two eye-antennal imaginal discs. Additionally, we find that Toll-2 regulates the timing of neck morphogenesis by promoting cell apoptosis and cell-cell rearrangements preceding neck folding. Last, we establish that Toll-2 independently and sequentially governs both homeotic compartment formation and the timing of its morphogenesis via PI3K and Src signaling, respectively. Altogether, our findings provide novel insights into the spatiotemporal regulation of homeotic compartment development.

developmental biology↗

bioRxiv2022

Homeotic compartment curvature and tension control spatiotemporal folding dynamics.

Shape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adult Drosophila head and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.

developmental biology↗