# Is Hydra Axis Definition a Fluctuation-Based Process Picking Up External Cues?

## TL;DR

This paper explains how Hydra regenerates its body axis using fluctuating gene activity and external cues like temperature gradients.

## Contribution

A novel theoretical model explains Hydra axis definition through gene expression fluctuations and mechanical signaling with minimal parameters.

## Key findings

- The model quantitatively reproduces the expression pattern of the gene ks1 during axis formation.
- Hydra's axis positioning is sensitive to weak temperature gradients in a non-intuitive way.
- Fluctuation-based symmetry breaking aligns with experimental findings on actin filaments and mechanical stimulation.

## Abstract

Axis definition plays a key role in the establishment of animal body plans, both in normal development and regeneration. The cnidarian Hydra can re-establish its simple body plan when regenerating from a random cell aggregate or a sufficiently small tissue fragment. At the beginning of regeneration, a hollow cellular spheroid forms, which then undergoes symmetry breaking and de novo body axis definition. In the past, we have published related work in a physics journal, which is difficult to read for scientists from other disciplines. Here, we review our work for readers not so familiar with this type of approach at a level that requires very little knowledge in mathematics. At the same time, we present a few aspects of Hydra biology that we believe to be linked to our work. These biological aspects may be of interest to physicists or members of related disciplines to better understand our approach. The proposed theoretical model is based on fluctuations of gene expression that are triggered by mechanical signaling, leading to increasingly large groups of cells acting in sync. With a single free parameter, the model quantitatively reproduces the experimentally observed expression pattern of the gene ks1, a marker for ‘head forming potential’. We observed that Hydra positions its axis as a function of a weak temperature gradient, but in a non-intuitive way. Supposing that a large fluctuation including ks1 expression is locked to define the head position, the model reproduces this behavior as well—without further changes. We explain why we believe that the proposed fluctuation-based symmetry breaking process agrees well with recent experimental findings where actin filament organization or anisotropic mechanical stimulation act as axis-positioning events. The model suggests that the Hydra spheroid exhibits huge sensitivity to external perturbations that will eventually position the axis.