Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy.

ABSTRACT: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of survival motor neuron (SMN) protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated patients with SMA, indicative of alterations in brain development. Here, using a mouse model of severe SMA, we revealed an underlying neurodevelopmental phenotype in SMA where prenatal SMN-dependent defects in translation drove disruptions in nonmotile primary cilia across the central nervous system (CNS). Low levels of SMN caused widespread perturbations in translation at E14.5 targeting genes associated with primary cilia. The de

SUBMITTER: Genovese F 

PROVIDER: S-EPMC12581668 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature