A topoietic model of collective morphogenesis and compartmentalization

Xenopus laevis embryos survive teratogenic stress at significantly higher rates in larger groups, a phenomenon termed cross-embryo morphogenetic assistance (CEMA) (Tung, Sperry et al. 2024). We introduce topoiesis , a proposed mechanism by which a constitutively secreted stress signal (extracellular ATP or adenosine) diffuses and decays across the group, accumulating more in larger groups where interior volume outpaces absorbing surface. We find that this rising field carries more embryos to survival and demarcates the collective more sharply from its surroundings as collective screening strength grows with size. At intermediate sizes the outcome is spatially organized (a rescued interior enclosed by a failing periphery) and reconstitutes after shuffling. In larger groups the field restructures: its peak concentration keeps rising while its interior gradient flattens into a near-uniform bulk bounded by a sharp rim, sharpening demarcation while blurring distinctions among interior members. This pre-pattern stabilizes well before individual fate commitment, opening a window in which collective geometry can act on survival outcome. A biophysically calibrated minimal model capturing these principles recapitulates CEMA rescue rates across all six observed group sizes ( N =1-306; 0%-92%) and the size-dependent craniofacial defect rate among survivors. It predicts that sealing a group's boundary against loss, rather than changing its size or biochemical regulation, moves mean rescue from 0% to 100% and reorganizes the rescue structure, tracking the predicted field geometry. These results reveal a hidden simplicity behind apparent complexity: diffusion and geometry alone may suffice to make a collective both spatially organized and controllable through macroscale intervention rather than microscale engineering of its members.

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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-11-04
DOI
https://doi.org/10.64898/2026.11.03.763900
Primary Topic
Developmental Biology and Gene Regulation
Type
preprint
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preprint

A topoietic model of collective morphogenesis and compartmentalization

Santosh Manicka, Michael Levin
bioRxiv (Cold Spring Harbor Laboratory)
Developmental Biology and Gene Regulation
preprint

A topoietic model of collective morphogenesis and compartmentalization

Santosh Manicka, Michael Levin
preprint en

Abstract

Xenopus laevis embryos survive teratogenic stress at significantly higher rates in larger groups, a phenomenon termed cross-embryo morphogenetic assistance (CEMA) (Tung, Sperry et al. 2024). We introduce topoiesis , a proposed mechanism by which a constitutively secreted stress signal (extracellular ATP or adenosine) diffuses and decays across the group, accumulating more in larger groups where interior volume outpaces absorbing surface. We find that this rising field carries more embryos to survival and demarcates the collective more sharply from its surroundings as collective screening strength grows with size. At intermediate sizes the outcome is spatially organized (a rescued interior enclosed by a failing periphery) and reconstitutes after shuffling. In larger groups the field restructures: its peak concentration keeps rising while its interior gradient flattens into a near-uniform bulk bounded by a sharp rim, sharpening demarcation while blurring distinctions among interior members. This pre-pattern stabilizes well before individual fate commitment, opening a window in which collective geometry can act on survival outcome. A biophysically calibrated minimal model capturing these principles recapitulates CEMA rescue rates across all six observed group sizes ( N =1-306; 0%-92%) and the size-dependent craniofacial defect rate among survivors. It predicts that sealing a group's boundary against loss, rather than changing its size or biochemical regulation, moves mean rescue from 0% to 100% and reorganizes the rescue structure, tracking the predicted field geometry. These results reveal a hidden simplicity behind apparent complexity: diffusion and geometry alone may suffice to make a collective both spatially organized and controllable through macroscale intervention rather than microscale engineering of its members.

bioRxiv (Cold Spring Harbor Laboratory)
Tufts University (US)
Developmental Biology and Gene Regulation
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