Abstract
Regulators of mitotic division, when dysfunctional or expressed in a deregulated manner (over- or underexpressed) in somatic cells, cause chromosome instability, which is a predisposing condition to cancer that is associated with unrestricted proliferation. Genes encoding mitotic regulators are growingly implicated in neurodevelopmental diseases. Here, we briefly summarize existing knowledge on how microcephaly-related mitotic genes operate in the control of chromosome segregation during mitosis in somatic cells, with a special focus on the role of kinetochore factors. Then, we review evidence implicating mitotic apparatus- and kinetochore-resident factors in the origin of congenital microcephaly. We discuss data emerging from these works, which suggest a critical role of correct mitotic division in controlling neuronal cell proliferation and shaping the architecture of the central nervous system.
Highlights
Regulators of the mitotic apparatus play key roles in orchestrating chromosome segregation.their coordinated activity is critical to the transmission of genetic stability throughout cell generations
Accurate chromosome segregation at cell division is fundamental to maintain the species chromosome number from one cell generation to the and prevent aneuploidy and chromosomal instability (CIN), which is commonly observed in cancer cells and is considered a driving force in the genesis and evolution of cancer [2,78]
Several mechanisms operate during spindle assembly to facilitate kinetochore–microtubule encounters [12], several erroneous kinetochore–microtubule interactions are formed, such as monotelic, syntelic, or merotelic interactions [81]
Summary
Regulators of the mitotic apparatus play key roles in orchestrating chromosome segregation Their coordinated activity is critical to the transmission of genetic stability throughout cell generations. The onset of mutations, or regulatory alterations (under- or overexpression) of mitotic factors in differentiated somatic tissues often leads to abnormal mitosis, the loss of checkpoint function, and the generation of genetically unbalanced daughter cells [1]. This favors the onset of conditions that predispose cells to become genetically unstable, which is one of the best-established cancer hallmarks and is associated with unrestrained proliferation [1,2]. We will confront some of the specificities and unresolved issues of mitotic dysfunction in the neuronal context
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