Cell-cell and cell-matrix adhesion regulated by Piezo1 is critical for stiffness-dependent DRG neuron aggregation
Mengshi Lei,
Weiyou Wang,
Hong Zhang,
Jihong Gong,
Zhili Wang,
Hanmian Cai,
Xiaofei Yang,
Shen Wang,
Cong Ma
Affiliations
Mengshi Lei
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Weiyou Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Hong Zhang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Jihong Gong
Key Laboratory of Cognitive Science, Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, South-Central Minzu University, Wuhan, China
Zhili Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Hanmian Cai
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Xiaofei Yang
Key Laboratory of Cognitive Science, Laboratory of Membrane Ion Channels and Medicine, College of Biomedical Engineering, South-Central Minzu University, Wuhan, China
Shen Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
Cong Ma
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Corresponding author
Summary: The dorsal root ganglion (DRG) is characterized by the dense clustering of primary sensory neuron bodies, with their axons extending to target tissues for sensory perception. The close physical proximity of DRG neurons facilitates the integration and amplification of somatosensation, ensuring normal physiological functioning. However, the mechanism underlying DRG neuron aggregation was unclear. In our study, we culture DRG neurons from newborn rats on substrates with varying stiffness and observe that the aggregation of DRG neurons is influenced by mechanical signals arising from substrate stiffness. Moreover, we identify Piezo1 as the mechanosensor responsible for DRG neurons’ ability to sense different substrate stiffness. We further demonstrate that the Piezo1-calpain-integrin-β1/E-cadherin signaling cascade regulates the aggregation of DRG neurons. These findings deepen our understanding of the mechanisms involved in histogenesis and potential disease development, as mechanical signals arising from substrate stiffness play a crucial role in these processes.
