MITOTIC PROTEINS IN BRAIN DEVELOPMENT: A DUAL PERSPECTIVE

Neurodevelopment depends on the precise coordination of proliferative expansion, differentiation, and maturation of neural cells. During early brain development, mitotic fidelity in neural progenitors is essential to ensure appropriate brain size, cellular diversity, and genomic stability. Consistently, mutations in genes encoding core mitotic regulators frequently lead to neurodevelopmental disorders. However, the resulting phenotypes are often selective and tissue-specific, rather than reflecting global proliferative failure, revealing a long-standing paradox in human genetics. This paradox supports a dual perspective on the role of mitotic proteins in neurodevelopment. On one hand, their canonical functions during cell division are critical for maintaining neural progenitor pools and preventing aneuploidy-associated developmental defects. On the other hand, expression patterns support that several mitotic regulators persist or are repurposed in post-mitotic neurons, where they contribute to processes independent of cell division. By integrating experimental data across complementary neurodevelopmental models, namely stem cell models, with bioinformatic analyses, this work provides convergent evidence supporting the dual roles of mitotic proteins in neurodevelopment.