| First Author | Ma S | Year | 2023 |
| Journal | Science | Volume | 379 |
| Issue | 6628 | Pages | 201-206 |
| PubMed ID | 36634173 | Mgi Jnum | J:334423 |
| Mgi Id | MGI:7428833 | Doi | 10.1126/science.add3598 |
| Citation | Ma S, et al. (2023) Excessive mechanotransduction in sensory neurons causes joint contractures. Science 379(6628):201-206 |
| abstractText | Distal arthrogryposis (DA) is a collection of rare disorders that are characterized by congenital joint contractures. Most DA mutations are in muscle- and joint-related genes, and the anatomical defects originate cell-autonomously within the musculoskeletal system. However, gain-of-function mutations in PIEZO2, a principal mechanosensor in somatosensation, cause DA subtype 5 (DA5) through unknown mechanisms. We show that expression of a gain-of-function PIEZO2 mutation in proprioceptive sensory neurons that mainly innervate muscle spindles and tendons is sufficient to induce DA5-like phenotypes in mice. Overactive PIEZO2 causes anatomical defects through increased activity within the peripheral nervous system during postnatal development. Furthermore, botulinum toxin (Botox) and a dietary fatty acid that modulates PIEZO2 activity reduce DA5-like deficits. This reveals a role for somatosensory neurons: Excessive mechanosensation within these neurons disrupts musculoskeletal development. |
