Fluid instabilities and active flows during vertebrate embryo body segmentation – Fidelio

One of the flourishing domains in modern developmental biology investigates the role of mechanical forces and biochemical signals in shaping embryonic tissues and driving the emergence of form. Somitogenesis in vertebrate embryos is a remarkable example, where a tissue—the presomitic mesoderm (PSM)—segments rhythmically into compact, regularly spaced structures called somites. These somites are essential building blocks for the spine and skeletal muscles. The process is periodic, robust, and evolutionarily conserved, yet the underlying mechanisms remain incompletely understood. While genetic regulation and biochemical signals have been studied in detail, the contribution of physical forces and their interplay with biochemical cues is far less explored.
FIDELIO brings a novel perspective by investigating somitogenesis not only as a gene-regulated process, but as a physical instability—akin to the Plateau-Rayleigh instability that causes liquid jets to break into droplets. We hypothesize that the PSM behaves as an “active fluid,” meaning that cells within the tissue consume energy to generate forces. As the tissue gradually epithelializes and its mechanical properties change, it may spontaneously become unstable and segment into somites. Understanding this process requires a combined experimental and theoretical approach.
To address this challenge, FIDELIO will develop an ex vivo novel biophysical platform using dissected chicken embryos, a well-established model for vertebrate development. We will build custom microfluidic devices to control the chemical environment of the tissue (such as gradients of morphogens like fibroblast growth factor and retinoic acid) and its physical constraints (such as adhesion and confinement). Live imaging and advanced microscopy will allow us to observe somite formation in real time and quantify how mechanical and chemical factors drive or inhibit segmentation.
In parallel, we will build a new generation of physical models to describe the behavior of the PSM as an active, heterogeneous material. These models will help interpret experimental results and predict how specific mechanical parameters—like viscosity, surface tension, and adhesion—affect tissue stability. Crucially, we will test these predictions experimentally, enabling an iterative feedback loop between theory and data.
The scientific impact of FIDELIO is twofold. First, it will shed light on the physical mechanisms that underpin a fundamental developmental process, offering a new perspective on how mechanical forces shape living tissues. Second, the project will create versatile tools—experimental and theoretical—for studying tissue segmentation and active matter. These tools can be applied to other biological contexts where tissue mechanics and reorganization play key roles, including organogenesis, regeneration, and cancer.
By bridging physics and developmental biology, FIDELIO aims to uncover general principles of tissue patterning, with the long-term potential to influence both basic research and biomedical applications.