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Sam68 expression declines postnatally while SLM2 increases after birth, and this developmental pattern is reinforced by hierarchical control of Sam68 expression by SLM2. Analysis of Sam68:Slm2 double knockout (Sam68:Slm2dko) mice revealed hundreds of exons that respond to joint depletion of these proteins. Moreover, parallel analysis of single and double knockout cortices indicated that exons regulated mainly by SLM2 are characterized by a dynamic splicing pattern during development, whereas Sam68-dependent exons are spliced at relatively constant rates. Dynamic splicing of SLM2-sensitive exons is completely suppressed in the Sam68:Slm2dko developing cortex. Sam68:Slm2dko mice die perinatally with defects in neurogenesis and in neuronal differentiation, and develop a hydrocephalus, consistent with splicing alterations in genes related to these biological processes. Thus, our study reveals that developmental control of separate Sam68 and Slm2 paralog genes encoding homologous RBPs enables the orchestration of a dynamic splicing program needed for brain development and viability, while ensuring a robust redundant mechanism that supports proper cortical development.<\/jats:p>","DOI":"10.1093\/nar\/gkae071","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T17:59:07Z","timestamp":1707328747000},"page":"4167-4184","source":"Crossref","is-referenced-by-count":5,"title":["Differential expression of paralog RNA binding proteins establishes a dynamic splicing program required for normal cerebral cortex development"],"prefix":"10.1093","volume":"52","author":[{"given":"Eleonora","family":"Cesari","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy, Catholic University of the Sacred Heart , Largo Francesco Vito 1 , 00168\u00a0 Rome , Italy"},{"name":"Fondazione Policlinico 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