Primary cilia as architects of the neocortex: Roles in brain development, function, and microcephaly.

The etiology of primary hereditary microcephaly (MCPH), a condition closely linked to neocortex development, remains poorly understood. Initially, MCPH genes were thought to regulate a limited set of cellular processes, but recent studies reveal that many encode multifunctional proteins, often converging on primary cilia, organelles that orchestrate the development of most vertebrate tissues and organs. In this perspective article, we examine the role of primary cilia in brain development and explore how disruptions in MCPH and microcephaly-associated proteins compromise ciliary dynamics and function. We highlight additional cilia-related proteins with potential influence on neurodevelopment. By elucidating the connections between primary cilia and neural development, we aim to provide insights into mechanisms of neuroregeneration. Ultimately, advancing our understanding of primary cilia may help develop therapeutic strategies to restore neuronal function and improve outcomes for individuals with neurodevelopmental disorders.KEYWORDSbrain development, microcephaly, neocortex, neural regeneration, neural stem cells, neurodevelopmental disorders, primary ciliaCopyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.