Biology subjects

Delpierre, J.

Publications and source records attributed to Delpierre, J..

4 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↗

bioRxiv2024

Hepatoblast iterative apicobasal polarization is regulated by extracellular matrix remodeling

Hepatocytes have a unique multiaxial polarity with several apical and basal surfaces. The prevailing model for the emergence of this multipolarity and the coordination of lumen formation between adjacent hepatocytes is based on asymmetric cell division. Here, investigating polarity generation in liver cell progenitors, the hepatoblasts, during liver development in vivo and in vitro, we found that this model cannot explain the observed dynamics of apical lumen formation in the embryonic liver. Instead, we identified a new mechanism of multi-axial polarization: We found that polarization can be initiated in a cell-autonomous manner by re-positioning apical recycling endosomes (AREs) to the cell cortex via fibronectin sensing through Integrin V. Using live cell imaging we showed that this process repeats, leading to multiaxial polarity independently of cell division. We found that establishment of oriented trafficking leads to secretion of the metalloprotease MMP13, allowing neighboring hepatoblasts to synchronize their polarization by sensing extracellular matrix (ECM) distribution and enabling lumen opening. Finally, active remodeling of ECM in proximity of nascent apical surfaces closes a positive feedback loop of polarization, whereas disruption of this loop by either blocking MMP13 or downregulating Integrin V prevents formation of the bile canaliculi network. Integration of this feedback loop into a simple mathematical model reproduces the observed dynamics of bile canaliculi network formation during liver development quantitatively. Our combined findings thus suggest a new mechanism of polarization coupling to self-organization at the tissue scale.

developmental biology↗

bioRxiv2021

Bulkhead-like apical membrane structures between hepatocytes are required for anisotropic lumen expansion and liver tissue morphogenesis

Lumen morphogenesis is key to the function of organs and results from the integration of molecular pathways and mechanical forces1-3. The mechanisms governing anisotropic lumen expansion remain elusive4-6. In contrast to epithelial cells which have simple apico-basal polarity and form tubes, hepatocytes are multi-polar and form narrow lumina that grow anisotropically between adjacent cells, collectively generating a complex 3D network of bile canaliculi (BC)7,8. Here, we studied lumen elongation and BC morphogenesis in differentiating primary mouse hepatoblasts in vitro. Remarkably, we discovered a pattern of specific extensions of the apical membrane traversing the lumen between adjacent hepatocytes and sealed by tight junctions, reminiscent of the bulkheads of boats. These structures were also present in the developing liver. A targeted screen revealed that silencing of Rab35 caused loss of the bulkheads, conversion of hepatocyte into simple epithelial polarity and formation of spherical lumina in vitro. Strikingly, we could re-engineer hepatocyte polarity and tissue morphogenesis in vivo in the embryonic liver, converting BC into simple epithelial tubes. Our results suggest that the apical bulkheads of hepatocytes are cell-intrinsic anisotropic mechanical elements that ensure stability of the elongating lumen between two cells, thus determining the structure of BC during liver tissue morphogenesis.

cell biology↗