Control of gastruloid patterning and morphogenesis by the Erk and Akt signaling pathways

Evan J. Underhill, Jared E. Toettcher

Research output: Contribution to journalArticlepeer-review

Abstract

Many developmental processes rely on the localized activation of receptor tyrosine kinases and their canonical downstream effectors Erk and Akt, yet the specific roles played by each of these signals is still poorly understood. Gastruloids, 3D cell culture models of mammalian gastrulation and axial elongation, enable quantitative dissection of signaling patterns and cell responses in a simplified, experimentally accessible context. We find that mouse gastruloids contain posterior-to-anterior gradients of Erk and Akt phosphorylation induced by distinct receptor tyrosine kinases, with features of the Erk pattern and expression of its downstream target Snail exhibiting hallmarks of size-invariant scaling. Both Erk and Akt signaling contribute to cell proliferation, whereas Erk activation is also sufficient to induce Snail expression and precipitate profound tissue shape changes. We further uncover that Erk signaling is sufficient to convert the entire gastruloid to one of two mesodermal fates depending on position along the anteroposterior axis. In all, these data demonstrate functional roles for two core signaling gradients in mammalian development and suggest how these modules might be harnessed to engineer user-defined tissues with predictable shapes and cell fates.

Original languageEnglish (US)
JournalDevelopment (Cambridge, England)
Volume150
Issue number16
DOIs
StatePublished - Aug 15 2023

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Keywords

  • Cell signaling
  • Gastruloid
  • Morphogenesis

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