[Seminar] "Phase transitions in early vertebrate development" by Prof. Carl-Philipp Heisenberg
Mechanosensation of tight junctions by ZO-1 phase separation and flow
Cell-cell junctions respond to mechanical forces by changing their organization and function. Tension-dependent conformational changes of junctional proteins are thought to underlie this junctional mechanosensitivity. Here we show that in the gastrulating zebrafish embryo, tight junctions (TJ) mechanosensitivity is mediated by actomyosin-driven flow of phase separated Zonula occludens-1 (ZO-1) clusters. We found that ZO-1 junctional accumulation at the contact between the Enveloping Layer (EVL) and the Yolk Syncytial Layer (YSL) closely scales with actomyosin tension. Actomyosin tension triggers ZO-1 junctional accumulation by driving retrograde actomyosin flow within the YSL that transport non-junctional ZO-1 clusters towards the TJ. Non-junctional ZO-1 clusters form by phase separation, and their effective formation is dependent on the actin binding region (ABR) within the C-terminus of ZO-1. If the non-junctional ZO-1 pool is absent, TJ lose their mechanosensitivity, and, consequently, EVL-YSL movement is impaired. Thus, phase separation and flow of nonjunctional ZO-1 confer mechanosensitivity to TJ.
Carl-Philipp Heisenberg holds Diplom in Biology from LMU Munich/Germany (1992), M.S. from University of Cambridge/UK (1993) and Ph.D. in Biology from RKU Tübingen/Germany (1997). He was a postdoc at UCL London/UK (1996-2000) and a Research Group Leader at the MPI-CBG Dresden/Germany (2001-2009). He joined IST Austria as Professor in 2009. His research focuses on the genetic, cellular and biophysical mechanisms underlying tissue morphogenesis in vertebrate development. He received an ERC Advanced Grant, the Lower Austria Science Prize and the Carus Medal of the German Academy of Sciences (Leopoldina).