PhD Exit Seminar for Yunyun Huang (Winklbauer Lab)

Prickle1 Regulates Cell Adhesion and Migration in the Xenopus laevis Gastrula

Abstract

Gastrulation is a series of morphogenetic movements that give rise to the primary germ layers. Molecular control of the process is an intriguing topic to understand how cell and tissue behaviour is coordinated. In the Xenopus gastrula, the prechordal mesoderm (PCM) undergoes involution, and it continues to move and spread along the ectoderm inner surface while it remains separate from it. The planar cell polarity (PCP) protein Prickle (Pk) is known to coordinate tissue polarity and has been implicated in regulating intercellular adhesion. In this thesis, I investigated Pk1’s role in controlling cell adhesion and motility in the PCM.

Pk1 is localized in both diffuse and punctate forms, and the former has been overlooked in most studies. I showed that diffuse Pk1 is ubiquitously expressed in the cytoplasm and is enriched in a sub-membrane zone that overlaps the cortex. I found that diffuse Pk1 is sufficient for up-regulating cortex F-actin, and this modulates cortex tension in the rearranging tissue. Pk1 acts in conjunction with another PCP component Dishevelled2, which antagonizes Pk1’s activity and down-regulates the cortex, and they share a common effector, Casein Kinase II. I proposed that diffuse Pk1 controls F-actin turnover below the cell membrane to modulate cortex density.

The PCM rearranges by differential cell-on-cell migration, and cells exhibit velocity gradients from deep tissue to mesoderm-ectoderm boundary. I showed that Pk1 coordinates cell polarity, morphology, orientation and neighbour exchange, and is necessary for generating the velocity gradients. PCM cell translocation is accompanied by lamellipodia formation and tail retraction, and both processes require Pk1. This control of cell motility could already be explained by diffuse Pk1-mediated cortex regulation, but punctate Pk1 may have additional roles, probably in dispersing local tension build-up. I found that Pk1 puncta can be induced by mechanical stresses, and they form at cell-cell contacts and at cell rear ends in vivo. I proposed that the puncta are not essential for PCM cell rearrangement, and they form as stress-induced by-products.

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Join Zoom Meeting

Wednesday, December 15^th, 2021 @ 2:10 PM

https://utoronto.zoom.us/j/88025566091

Meeting ID: 880 2556 6091

Host: Rudi Winklbauer (r.winklbauer@utoronto.ca)

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