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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.
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Anterior–posterior pattern formation in ciliates
Abstract As single cells, ciliates build, duplicate, and even regenerate complex cortical patterns by largely unknown mechanisms that precisely position organelles along two cell‐wide axes: anterior–posterior and circumferential (left–right). We review our current understanding of intracellular patterning along the anterior–posterior axis in ciliates, with emphasis on how the new pattern emerges during cell division. We focus on the recent progress at the molecular level that has been driven by the discovery of genes whose mutations cause organelle positioning defects in the model ciliateTetrahymena thermophila. These investigations have revealed a network of highly conserved kinases that are confined to either anterior or posterior domains in the cell cortex. These pattern‐regulating kinases create zones of cortical inhibition that by exclusion determine the precise placement of organelles. We discuss observations and models derived from classical microsurgical experiments in large ciliates (includingStentor) and interpret them in light of recent molecular findings inTetrahymena. In particular, we address the involvement of intracellular gradients as vehicles for positioning organelles along the anterior‐posterior axis.
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- Award ID(s):
- 1947608
- PAR ID:
- 10378162
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Journal of Eukaryotic Microbiology
- Volume:
- 69
- Issue:
- 5
- ISSN:
- 1066-5234
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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