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How simple physics drives the earliest stages of embryogenesis

Created on 09 Jan 2026

Authors

Cockerell, A., Shadmani, P., Tsaneva-Atanasova, K., Richards, D. M.

Abstract

The initial stages of mammalian embryo development involve a single fertilised egg that repeatedly divides to create a solid ball of cells called a morula. Despite the apparent simplicity of this process, which involves only one cell type and a few tens of cells, there are still a host of unanswered questions, particularly around the underlying biophysical mechanisms that are at play. To address this, we here develop a novel type of vertex model that includes cortical tension, cell-to-cell adhesion, membrane curvature and cell volume forces, along with a zona pellucida, cell division and the effect of noise. We fit our model to both mouse and human experimental data, which allows us to address a number of key questions including the relative roles of adhesion and tension, how the cortical tension varies around the cell, the purpose of the zona pellucida, and the rules governing the first few cell divisions. We also determine the biophysical effects responsible for compaction and internalisation, including addressing why the morula does not typically decompact during internalisation. Next, we investigate the position-versus-polarisation debate during trophectoderm differentiation, how the division axis is determined during later divisions, and the role of noise. Finally, we compare human and mouse, focussing on the key similarities that may span all mammals. Our use of a force-based computational model allows us to address fundamental questions relating to mammalian development, particularly the underlying biophysical rules governing early embryogenesis, with important applications to stem cell models such as blastoids, conservation efforts of endangered species and embryo grading during IVF.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 09 Jan 2026.

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