PUBLICATION

Mechanically sensitive HSF1 is a key regulator of left-right symmetry breaking in zebrafish embryos

Authors
Du, J., Li, S.K., Guan, L.Y., Guo, Z., Yin, J.F., Gao, L., Kawanishi, T., Shimada, A., Zhang, Q.P., Zheng, L.S., Liu, Y.Y., Feng, X.Q., Zhao, L., Chen, D.Y., Takeda, H., Fan, Y.B.
ID
ZDB-PUB-231002-175
Date
2023
Source
iScience   26: 107864107864 (Journal)
Registered Authors
Takeda, Hiroyuki
Keywords
Cell biology, Developmental biology, Embryology, Molecular biology
MeSH Terms
none
PubMed
37766982 Full text @ iScience
Abstract
The left-right symmetry breaking of vertebrate embryos requires nodal flow. However, the molecular mechanisms that mediate the asymmetric gene expression regulation under nodal flow remain elusive. Here, we report that heat shock factor 1 (HSF1) is asymmetrically activated in the Kupffer's vesicle 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 is a mechanosensitive protein. The mechanical sensation ability of HSF1 is conserved in a variety of mechanical stimuli in different cell types. Moreover, cilia and 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 by mechanical clues during embryonic development and other physiological and pathological transformations.
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Human Disease / Model
Sequence Targeting Reagents
Fish
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Engineered Foreign Genes
Mapping