Multifaceted Microcephaly-Related Gene MCPH1

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 2; p. 275
• Main Authors: Kristofova, Martina, Ori, Alessandro, Wang, Zhao-Qi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.01.2022; MDPI
• Subjects: Amino acids; Animal models; Animals; Apoptosis; Brain - pathology; Cell cycle; Cell proliferation; Cell self-renewal; Chromosomes; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Disease Models, Animal; DNA damage; DNA repair; Genes; Genetic Predisposition to Disease; gonad development; Humans; Mammals; MCPH; Microcephaly; Microcephaly - genetics; Microencephaly; mouse models; Mutation; Neural stem cells; Neurodevelopmental disorders; Neurogenesis; Neurogenesis - genetics; Neurons; Proteins; Review; Tumorigenesis; mouse models; neurogenesis; gonad development; MCPH; tumorigenesis
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11020275

MCPH1, or BRIT1, is often mutated in human primary microcephaly type 1, a neurodevelopmental disorder characterized by a smaller brain size at birth, due to its dysfunction in regulating the proliferation and self-renewal of neuroprogenitor cells. In the last 20 years or so, genetic and cellular studies have identified MCPH1 as a multifaceted protein in various cellular functions, including DNA damage signaling and repair, the regulation of chromosome condensation, cell-cycle progression, centrosome activity and the metabolism. Yet, genetic and animal model studies have revealed an unpredicted essential function of MPCH1 in gonad development and tumorigenesis, although the underlying mechanism remains elusive. These studies have begun to shed light on the role of MPCH1 in controlling various pathobiological processes of the disorder. Here, we summarize the biological functions of MCPH1, and lessons learnt from cellular and mouse models of MCPH1.