Speaker: Crystal Rogers, University of California, Davis, associate professor in anatomy, physiology and cell biology

Title: Tubulin β-III drives neural crest cell state changes during EMT

Abstract: The epithelial-to-mesenchymal transition (EMT) requires rapid and reversible remodeling of cell adhesion, polarity, and cytoskeletal architecture. Although transcriptional programs governing EMT are well defined, how these transitions are executed at the level of cytoskeletal organization in vivo remains poorly understood. Using the Gallus gallus (chick) neural crest (NC) model, we identify microtubule composition as a key post-translational regulator of EMT. Single-cell RNA sequencing reveals dynamic and cell state-specific expression of α- and β-tubulin isotypes during NC development, including enrichment of TUBB3, TUBA3E, and TUBG1 in NC populations. Spatial validation by in situ hybridization chain reaction (HCR) demonstrates that these expression patterns are tightly coordinated with EMT and migratory states, while concurrent expression of microtubule motor genes (KIF11, DYNC1LI1) suggests coupling between microtubule architecture and cargo transport capacity. Functionally, we show that the highly dynamic β-tubulin isotype TUBB3 is both necessary and sufficient to drive cellular remodeling. Loss of TUBB3 stabilizes adherens junctions, maintains epithelial polarity, and arrests EMT, whereas TUBB3 overexpression induces cytosolic E-cadherin accumulation, mitotic defects, and aberrant neural tube morphogenesis. We further find that EMT progression is accompanied by redistribution of detyrosinated microtubules, a modification retained in EMT-arrested cells, indicating layered regulation of microtubule function. Together, these findings support a model in which EMT is encoded through systematic reprogramming of microtubule composition and decoded via motor-mediated trafficking of adhesion components. In addition to defining a mechanistic role for tubulin isotypes in controlling cell state transitions, this work provides a spatiotemporal atlas of cytoskeletal gene expression as a resource for investigating how microtubule architecture directs developmental and disease-associated EMT.

Host: Dior Kelley, GDCB associate professor