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bioRxiv · 10.64898/2026.04.24.720339

Quantitative multi-scale morphodynamic analysis reveals ratchet-like collective DVE migration and epiblast retrograde cell flow during anterior patterning in the mouse embryo

Stower, M. J.·Zhou, F. Y.·Valani, R.·Rozman, J.·Hathrell, H.·Godwin, J.·Lu, X.·Rittscher, J.·Yeomans, J. M.·Srinivas, S.
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Abstract

The collective unidirectional migration of distal visceral endoderm (DVE) cells in the early mouse embryo is required to pattern the anterior-posterior (A-P) axis in the epiblast. It is unknown to what extent A-P axial asymmetries exist prior to DVE migration, how migration becomes channeled towards one side of the embryo, and whether the epiblast cells they migrate over have coordinated movements. We developed a quantitative embryo-wide, tissue-tracking approach to analyse visceral endoderm and epiblast tissue morphodynamics in a longitudinal light-sheet imaged, multi-embryo data-set. Here we show that asymmetric morphology of the ectoplacental cone already present prior to DVE migration correlates with the alignment of the A-P axis but not its polarity. DVE cell movements are initiated with a relatively low cell coordination and small net migration, then get channelled in an abrupt transition to a highly coordinated, uni-directional anterior motion. This anteriorwards migration is characterised by a ratchet-like, intermittent motion. Vertex modelling demonstrates that tissue rheology can account for DVE start-stop motion, and suggests that T1-mediated stress relaxation in the surrounding tissue can facilitate intermittent DVE motion without requiring intrinsic fluctuations in DVE velocity. Finally, comparing cell movement of the DVE with the underlying epiblast reveals a previously unknown coordinated motion in the anterior epiblast, opposite to the direction of DVE migration. Together these data provide insights into the origin of embryonic axial asymmetry and a previously unappreciated coordination between VE and epiblast tissue-motion during anterior-posterior patterning. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/720339v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1cfe4fdorg.highwire.dtl.DTLVardef@1c2c3e6org.highwire.dtl.DTLVardef@1cb6a5corg.highwire.dtl.DTLVardef@1b3ed19_HPS_FORMAT_FIGEXP M_FIG C_FIG See supplemental movie: animated abstract

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Stower, M. J., Zhou, F. Y., Valani, R., Rozman, J., Hathrell, H., Godwin, J., Lu, X., Rittscher, J., Yeomans, J. M., Srinivas, S.. 2026-04-28. Quantitative multi-scale morphodynamic analysis reveals ratchet-like collective DVE migration and epiblast retrograde cell flow during anterior patterning in the mouse embryo. https://doi.org/10.64898/2026.04.24.720339

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