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In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cell (MPC)-specific SMN-depleted mouse models, we reveal that SMN reduction in limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ). Specifically, these mice exhibited impaired growth plate homeostasis and reduced insulin-like growth factor (IGF) signaling from chondrocytes, rather than from the liver. Furthermore, the reduction of SMN in fibro-adipogenic progenitors (FAPs) resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis of SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.<\/jats:p>","DOI":"10.7554\/elife.92731","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T06:21:26Z","timestamp":1699338086000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92731","source":"Crossref","is-referenced-by-count":7,"title":["Depletion of SMN protein in mesenchymal progenitors impairs the development of bone and neuromuscular junction in spinal muscular atrophy"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0871-3414","authenticated-orcid":true,"given":"Sang-Hyeon","family":"Hann","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04h9pn542","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences, Seoul National University","place":["Seoul, 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