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bioRxiv · 10.64898/2026.10.19.760207

APLNR regulates directed migration to spatially pattern mesoderm in human gastruloids

Johnson, A. B.·Seetharaman, S.·Plum, A. M.·Yao, L.·Yu, Z.·Serra, M.·Heemskerk, I.·Gardel, M.
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Abstract

During human gastrulation, mesoderm progenitors migrate while acquiring distinct identities. Whether this movement contributes to subsequent patterning remains unclear. Here, we identify the apelin receptor (APLNR) as a regulator of directed migration of mesoderm in human gastruloids. TBXT+ cells ingress basally and disperse from the PS-like region toward epiblast-like cells. Tracking reveals that this dispersal reflects a directional bias rather than increased speed. APLNR is enriched in nascent mesoderm, while its ligand APELA is expressed in adjacent epithelial cells. Control gastruloids exhibit fourfold greater dispersal than APLNR-depleted gastruloids despite modest speed differences, consistent with a model of chemotaxis by an epithelial ligand field. Paraxial and lateral mesoderm differentiation competence is preserved following APLNR depletion, while signaling programs and central FOXC2+ paraxial organization are altered. These findings support a role for APLNR-dependent guidance in positioning competent mesoderm progenitors for subsequent patterning.

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Johnson, A. B., Seetharaman, S., Plum, A. M., Yao, L., Yu, Z., Serra, M., Heemskerk, I., Gardel, M.. 2026-10-20. APLNR regulates directed migration to spatially pattern mesoderm in human gastruloids. https://doi.org/10.64898/2026.10.19.760207

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