biostudies-literatureUnknown6(3)Inaguma YMarinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 mutations in abnormal corticogenesis of MSS. SIL1-silencing caused neuronal migration delay during corticogenesis ex vivo. While RNAi-resistant SIL1 rescued the defects, three MSS-causing SIL1 mutants tested did not. These mutants had lower affinities to HSPA5 in vitro, and SIL1-HSPA5 interaction as well as HSPA5 function was found to be crucial for neuronal migration ex vivo. Furthermore time-lapse imaging revealed morphological disorganization associated with abnormal migration EMBO molecular medicine414-29https://www.ebi.ac.uk/biostudies/studies/S-EPMC3958314biostudies-literatureSIL1, a causative cochaperone gene of Marinesco-Sojgren syndrome, plays an essential role in establishing the architecture of the developing cerebral cortex.PMC3958314Morishita RSuzuki MTabata HIwamoto IIto HNishimura YVMizuno MOhno KKumagai TNagata KInaguma YHamada NfalseSIL1, a causative cochaperone gene of Marinesco-Sojgren syndrome, plays an essential role in establishing the architecture of the developing cerebral cortex.Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 mutations in abnormal corticogenesis of MSS. SIL1-silencing caused neuronal migration delay during corticogenesis ex vivo. While RNAi-resistant SIL1 rescued the defects, three MSS-causing SIL1 mutants tested did not. These mutants had lower affinities to HSPA5 in vitro, and SIL1-HSPA5 interaction as well as HSPA5 function was found to be crucial for neuronal migration ex vivo. Furthermore time-lapse imaging revealed morphological disorganization associated with abnormal migration 2014-01-01T00:00:00Z2014 Mar2026-04-16T09:11:38.487Z2019-03-27T01:23:39ZS-EPMC39583142447320010.1002/emmm.201303069