{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:27:00Z","timestamp":1790879220721,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T00:00:00Z","timestamp":1248825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2010,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Deletions or mutations in <jats:italic>survival of motor neuron 1<\/jats:italic> (<jats:italic>SMN1<\/jats:italic>) cause motor neuron loss and spinal muscular atrophy (SMA), a neuromuscular disorder, with the most severe type manifesting in utero. Whether SMA is a disease of defects in neurodevelopment and\/or neuromaintenance remains unclear. We performed an analysis of <jats:italic>Smn<\/jats:italic> gene and protein expression during murine embryogenesis. Furthermore, we examined <jats:italic>Smn<jats:sup>\u2212\/\u2212<\/jats:sup>;SMN2<\/jats:italic> mice, a model of very severe SMA, for developmental, morphological, and molecular abnormalities. We demonstrate that <jats:italic>Smn<\/jats:italic> transcript levels are regulated in a tissue\u2010 and developmental stage\u2010specific manner and that the Smn protein expression pattern generally followed that of the <jats:italic>Smn<\/jats:italic> mRNA. Cell death and pathological foci were observed in E10.5 Smn\u2010depleted embryos, and this increased in the telencephalon at E14.5. Furthermore, we show an altered morphology of cranial nerves as well as truncated lumbar spinal nerves in a subset of E10.5 <jats:italic>Smn<jats:sup>\u2212\/\u2212<\/jats:sup>;SMN2<\/jats:italic> embryos. Finally, we compared the splicing of a subset of genes shown recently to be aberrantly spliced in phenotypic\u2010stage SMA mice. Changes in alternative splicing of the <jats:italic>Slc38a5<\/jats:italic> and <jats:italic>Uspl1<\/jats:italic> genes were detectable in prephenotypic\u2010stage embryos and neonates but became more pronounced with the severity of the phenotype. By comparison, <jats:italic>Hif3a<\/jats:italic> alternative splicing was affected only at the end stage of disease. This result suggests that alterations in mRNA splicing in SMA occur, in part, as a result of disease progression. Overall, we conclude that Smn depletion affects developmental processes, which ultimately may also contribute to SMA pathogenesis. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.22189","type":"journal-article","created":{"date-parts":[[2009,7,29]],"date-time":"2009-07-29T17:04:01Z","timestamp":1248887041000},"page":"111-122","source":"Crossref","is-referenced-by-count":44,"title":["Neurodevelopmental consequences of Smn depletion in a mouse model of spinal muscular atrophy"],"prefix":"10.1002","volume":"88","author":[{"given":"Hong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Shafey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin 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