Abstract
Primary microcephaly is a brain growthdisorder characterized by a severe reduction of brain size and thinning of the cerebral cortex. Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development. Centrosomes are microtubule organizing centers that participate in several processes, including controlling polarity, catalyzing spindle assembly in mitosis, and building primary cilia. Understanding which of these processes are altered and how these disruptions contribute to microcephaly pathogenesis is a central unresolved question. In this review, we revisit the different models that have been proposed to explain howcentrosome dysfunction impairs cortical development. We review the evidence supporting a unified model in which centrosome defects reduce cell proliferation in the developing cortex by prolonging mitosis and activating a mitotic surveillance pathway. Finally, wealso extend our discussion to centrosomeindependent microcephaly mutations, such as those involved in DNA replication and repair.
Original language | English (US) |
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Pages (from-to) | 1551-1578 |
Number of pages | 28 |
Journal | Genes and Development |
Volume | 35 |
Issue number | 23-24 |
DOIs | |
State | Published - Dec 1 2021 |
Keywords
- Brain development
- Centriole
- Centrosome
- Cilia
- Microcephaly
ASJC Scopus subject areas
- Genetics
- Developmental Biology