Biology subjects

Plum, A. M.

Publications and source records attributed to Plum, A. M..

5 recordsLinked to original sources

bioRxiv2026

APLNR regulates directed migration to spatially pattern mesoderm in human gastruloids

During human gastrulation, mesoderm progenitors migrate while acquiring distinct identities. Whether this movement contributes to subsequent patterning remains unclear. Here, we identify the apelin receptor (APLNR) as a regulator of directed migration of mesoderm in human gastruloids. TBXT+ cells ingress basally and disperse from the PS-like region toward epiblast-like cells. Tracking reveals that this dispersal reflects a directional bias rather than increased speed. APLNR is enriched in nascent mesoderm, while its ligand APELA is expressed in adjacent epithelial cells. Control gastruloids exhibit fourfold greater dispersal than APLNR-depleted gastruloids despite modest speed differences, consistent with a model of chemotaxis by an epithelial ligand field. Paraxial and lateral mesoderm differentiation competence is preserved following APLNR depletion, while signaling programs and central FOXC2+ paraxial organization are altered. These findings support a role for APLNR-dependent guidance in positioning competent mesoderm progenitors for subsequent patterning.

developmental biology↗

bioRxiv2026

Positional information and information flows in dynamic tissues

During development, embryos store, transmit, and transform information to generate spatial patterns. Positional information (PI) quantifies how precisely cells form patterns at a given time, but cell motion has limited its application to static tissues. We introduce a framework for PI in dynamic tissues by decomposing mutual information between cells positions and properties over time into information flows contributing to PI preservation, loss and generation. These reveal information-theoretic signatures of ubiquitous developmental processes, including instruction, sorting and mixing, directly from data. Applying this framework to whole-embryo cell trajectories in Drosophila, mouse and zebrafish gastrulation, we provide local and global information-theoretic quantification of cell mixing and derive bounds on PI preservation imposed by tissue dynamics. Analyzing tissue flows as dynamical systems, we further show that morphogenesis structures mixing, preferentially preserving specific patterns. Finally, we derive inequality conditions for tracing generated PI to candidate information sources and distinguishing among alternative pattern-formation mechanisms, from programmed extracellular cues to self-organizing intercellular interactions.

biophysics↗

bioRxiv2025

Conditions enabling the persistence of cooperating ribozymes without cellular encapsulation

Explaining the origin of molecular systems composed of cooperating polymer sets that confer both metabolic and information processing functions is a key challenge in origins-of-life research. A related puzzle is the emergence of polymers of sufficient length to confer complex functions such as the RNA-dependent RNA polymerization with proofreading. Addressing these issues using computational models of template-guided replicating polymer systems is generally constrained by the exponential increase in diversity as the length of polymers increases. In this study, inspired by the computer game Tetris(R) and the Polymerase Chain Reaction (PCR) technique, we developed an abstract computational model of cooperative replicating polymer systems that avoids tracking all potential sequences. Using this model, we explored cooperative chemical ecosystems consisting of catalytic polymers conferring functions analogous to kinases, ligases, and mutation inhibitors. We show that prebiotic environments with micro-compartments with local exchanges enable multilevel selection that facilitates the survival of cooperating polymers. The ability of cooperative systems to persist is sensitive to intrinsic properties of catalysts such as catalytic efficiency and extrinsic factors such as dilution rate. These results provide a roadmap for future studies that look not just at persistence but also at the stepwise, de novo emergence of chemical ecosystems with both metabolic and information-processing capabilities.

evolutionary biology↗

bioRxiv2025

Morphogen Patterning in Dynamic Tissues

Embryogenesis integrates morphogenesis--coordinated cell movements--with morphogen patterning and cell differentiation. While largely studied independently, morphogenesis and patterning often unfold simultaneously in early embryos. Yet, how cell movements affect patterning remains unclear, as most pattern formation models assume static tissues. We address this gap by developing a mathematical framework for morphogen patterning in dynamic tissues, reformulating advection-reaction-diffusion models in cells reference frames--the most natural for signal interpretation and fate decisions. This framework (i) elucidates how morphogenesis mediates morphogen transport and compartmentalization: multicellular attractors enhance cell-cell diffusive transport, while repellers act as barriers, affecting cell fate induction and bifurcations. (ii) It formalizes cell-cell signaling ranges in dynamic tissues, deconfounding morphogenetic movements and identifying which cells can communicate. (iii) It provides two nondimensional numbers--typically distinct from the Peclet number--to assess when and where morphogenesis is relevant for patterning. (iv) It elucidates the generative role of cell density dynamics in patterning. We apply this framework to classic patterning models, morphogenetic motifs, and avian gastrulation data. Broadly, our work provides a quantitative perspective to rationalize dynamic tissue patterning in natural and synthetic embryos.

developmental biology↗

bioRxiv2024

Control of Modular Tissue Flows Shaping the Embryo in Avian Gastrulation

Avian gastrulation requires coordinated flows of thousands of cells to form the body plan. We quantified these flows using their fundamental kinematic units: one attractor and two repellers constituting its Dynamic Morphoskeleton (DM). We have also elucidated the mechanistic origin of the attractor, marking the primitive streak (PS), and controlled its shape, inducing gastrulation flows in the chick embryo that are typical of other vertebrates. However, the origins of repellers and dynamic embryo shape remain unclear. Here, we address these questions using active matter physics and experiments. Repeller 1, separating the embryo proper (EP) from extraembryonic (EE) tissues, arises from the tug-of-war between EE epiboly and EP isotropic myosin-induced active stress. Repeller 2, bisecting the anterior and posterior PS and associated with embryo shape change, arises from anisotropic myosin-induced active intercalation in the mesendoderm. Combining mechanical confinement with inhibition of mesendoderm induction, we eliminated either one or both repellers, as predicted by our model. Our results reveal a remarkable modularity of avian gastrulation flows delineated by the DM, uncovering the mechanistic roles of EE epiboly, EP active constriction, mesendoderm intercalation and ingression. These findings offer a new perspective for deconstructing morphogenetic flows, uncovering their modular origin, and aiding synthetic morphogenesis.

developmental biology↗