Biology subjects

Trenado-Yuste, C.

Publications and source records attributed to Trenado-Yuste, C..

3 recordsLinked to original sources

bioRxiv2026

TGFβ determines epithelial tissue spacing by regulating mesenchymal condensation

The branched structure of the vertebrate lung provides a high surface area-to-volume ratio, which increases the efficiency of diffusion-driven gas exchange. Generating this structure requires that the epithelial branches avoid contacting each other as they elongate during development. Previous studies have suggested that the spacing between neighboring branches is intrinsic to growth of the epithelium, but the underlying physical mechanisms remain elusive. Here, we used the embryonic chicken lung as a model system and found that branch spacing is regulated primarily by signaling to the mesenchyme through transforming growth factor-beta (TGF{beta}). Although proliferation decreases in epithelial cells that are located in close proximity to an adjacent branch, these patterns surprisingly emerge after regular branch spacing has been established. Instead, we find that TGF{beta} promotes the directed migration of mesenchymal cells, which form a condensation that physically displaces the adjacent epithelium and tunes branch spacing. Continuous disruption of TGF{beta} signaling prevents mesenchymal condensation and eventually results in contact between adjacent branches. These data suggest that the spacing between epithelial branches results from mesenchymal cell dynamics rather than from epithelial-intrinsic self-avoidance.

developmental biology↗

bioRxiv2023

Interfacial morphodynamics of proliferating microbial communities

In microbial communities, various cell types often coexist by occupying distinct spatial domains. What determines the shape of the interface between such domains--which in turn influences the interactions between cells and overall community function? Here, we address this question by developing a continuum model of a 2D spatially-structured microbial community with two distinct cell types. We find that, depending on the balance of the different cell proliferation rates and substrate friction coefficients, the interface between domains is either stable and smooth, or unstable and develops finger-like protrusions. We establish quantitative principles describing when these different interfacial behaviors arise, and find good agreement both with the results of previous experimental reports as well as new experiments performed here. Our work thus helps to provide a biophysical basis for understanding the interfacial morphodynamics of proliferating microbial communities, as well as a broader range of proliferating active systems.

biophysics↗

bioRxiv2022

Vangl facilitates mesenchymal thinning during lung sacculation independently of Celsr

The planar cell polarity (PCP) complex orients cytoskeletal and multicellular organization throughout vertebrate development. PCP is speculated to function in formation of the murine lung, where branching morphogenesis generates a complex tree of tubular epithelia whose distal tips expand dramatically during sacculation in preparation for gas exchange after birth. Here, using tissue-specific knockouts, we show that the PCP complex is dispensable in the airway epithelium for sacculation. Rather, we find a novel, Celsr1-independent role for the PCP component Vangl in the pulmonary mesenchyme: loss of Vangl1/2 inhibits mesenchymal thinning and expansion of the saccular epithelium. Further, loss of mesenchymal Wnt5a mimics the sacculation defects observed in Vangl2-mutant lungs, implicating mesenchymal Wnt5a/Vangl signaling as a key regulator of late lung morphogenesis. By mathematically modeling sacculation, we predict that the process of sacculation requires a fluid mesenchymal compartment. Finally, lineage-tracing and cell-shape analyses are consistent with the pulmonary mesenchyme acting as a fluid tissue, and suggest that loss of Vangl1/2 likely impacts the ability of mesenchymal cells to exchange neighbors. Our data thus uncover an explicit function for Vangl and the pulmonary mesenchyme during late lung morphogenesis to actively shape the saccular epithelium.

developmental biology↗