The impact of RASopathy-associated mutations on CNS development in mice and humans

• Main Authors: Minkyung Kang, Yong-Seok Lee
• Format: Article
• Language: English
• Published: BMC 2019-11-01
• Series: Molecular Brain
• Subjects: RAS; MAPK; neurodevelopmental disorders; cognition; mutant strains mouse
• Online Access: http://link.springer.com/article/10.1186/s13041-019-0517-5

Abstract The RAS signaling pathway is involved in the regulation of developmental processes, including cell growth, proliferation, and differentiation, in the central nervous system (CNS). Germline mutations in the RAS signaling pathway genes are associated with a group of neurodevelopmental disorders, collectively called RASopathy, which includes neurofibromatosis type 1, Noonan syndrome, cardio-facio-cutaneous syndrome, and Costello syndrome. Most mutations associated with RASopathies increase the activity of the RAS-ERK signaling pathway, and therefore, most individuals with RASopathies share common phenotypes, such as a short stature, heart defects, facial abnormalities, and cognitive impairments, which are often accompanied by abnormal CNS development. Recent studies using mouse models of RASopathies demonstrated that particular mutations associated with each disorder disrupt CNS development in a mutation-specific manner. Here, we reviewed the recent literatures that investigated the developmental role of RASopathy-associated mutations using mutant mice, which provided insights into the specific contribution of RAS-ERK signaling molecules to CNS development and the subsequent impact on cognitive function in adult mice.