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Mechanically Sensitive HSF1 is a Key Regulator of Left-Right Symmetry Breaking in Zebrafish Embryos

By Jing Du, Shu Kai Li, Liu-Yuan Guan, Zheng Guo, Jang-Fan Yin, Li Gao, Toru Kawanishi, Atsuko Shimada, Qiu-ping Zhang, Li-Sha Zheng, Yi-Yao Liu, Xi-Xiao Feng, Dong-Yan Chen, Hiroyuki Takeda, Yubo Fan

Posted 25 Feb 2021
bioRxiv DOI: 10.1101/2021.02.25.432863

The left-right symmetry breaking of vertebrate embryos requires fluid flow (called nodal flow in zebrafish). However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. In this paper, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kuppfer's vesicle at the early stage of zebrafish embryos in the presence of nodal flow. Deficiency in HSF1 expression caused a significant situs inversus and disrupted gene expression asymmetry of nodal signaling proteins in zebrafish embryos. Further studies demonstrated that HSF1 could be immediately activated by fluid shear stress. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and the Ca2+-Akt signaling axis are essential for the activation of HSF1 under mechanical stress in vitro and in vivo. Considering the conserved expression of HSF1 in organisms, these findings unveil a fundamental mechanism of gene expression regulation triggered by mechanical clues during embryonic development and other physiological and pathological transformations

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