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bioRxiv · 10.1101/2023.07.24.550374

TIAM-1 regulates polarized protrusions during dorsal intercalation in the C. elegans embryo through both its GEF and N-terminal domains

Zhu, Y.·Hardin, J.
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Abstract

Mediolateral cell intercalation is a morphogenetic strategy used throughout animal development to reshape tissues. Dorsal intercalation in the C. elegans embryo involves the mediolateral intercalation of two rows of dorsal epidermal cells to create a single row that straddles the dorsal midline, and so is a simple model to study cell intercalation. Polarized protrusive activity during dorsal intercalation requires the C. elegans Rac and RhoG orthologs CED-10 and MIG-2, but how these GTPases are regulated during intercalation has not been thoroughly investigated. In this study, we characterize the role of the Rac-specific guanine nucleotide exchange factor (GEF), TIAM-1, in regulating actin-based protrusive dynamics during dorsal intercalation. We find that TIAM-1 can promote protrusion formation through its canonical GEF function, while its N-terminal domains function to negatively regulate this activity, preventing the generation of ectopic protrusions in intercalating cells. We also show that the guidance receptor UNC-5 inhibits ectopic protrusive activity in dorsal epidermal cells, and that this effect is in part mediated via TIAM-1. These results expand the network of proteins that regulate basolateral protrusive activity during directed cell rearrangement. Summary statementTIAM-1 activates the Rac pathway to promote protrusion formation via its GEF domain, while its N-terminal domains suppress ectopic protrusions during dorsal intercalation in the C. elegans embryo.

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Zhu, Y., Hardin, J.. 2023-07-24. TIAM-1 regulates polarized protrusions during dorsal intercalation in the C. elegans embryo through both its GEF and N-terminal domains. https://doi.org/10.1101/2023.07.24.550374

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