Du Jing, Li Shu-Kai, Guan Liu-Yuan, Guo Zheng, Yin Jiang-Fan, Gao Li, Kawanishi Toru, Shimada Atsuko, Zhang Qiu-Ping, Zheng Li-Sha, Liu Yi-Yao, Feng Xi-Qiao, Zhao Lin, Chen Dong-Yan, Takeda Hiroyuki, Fan Yu-Bo
Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China.
Institute of Biomechanics and Medical Engineering, Department of Mechanical Engineering, School of Aerospace, Tsinghua University, Beijing 100084, China.
iScience. 2023 Sep 9;26(10):107864. doi: 10.1016/j.isci.2023.107864. eCollection 2023 Oct 20.
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 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 Ca-Akt signaling axis are essential for the activation of HSF1 under mechanical stress and . 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.
脊椎动物胚胎的左右对称破缺需要节点流。然而，在节点流作用下介导不对称基因表达调控的分子机制仍不清楚。在此，我们报告热休克因子1（HSF1）在存在节点流的斑马鱼胚胎的库普弗小泡中被不对称激活。HSF1表达缺陷导致斑马鱼胚胎中节点信号蛋白的基因表达显著且紊乱的不对称性。进一步研究表明HSF1是一种机械敏感蛋白。HSF1的机械感知能力在不同细胞类型的多种机械刺激中保守存在。此外，纤毛和Ca-Akt信号轴对于机械应力下HSF1的激活至关重要。考虑到HSF1在生物体内的保守表达，这些发现揭示了胚胎发育以及其他生理和病理转变过程中机械线索调控基因表达的基本机制。
