An intimate link between centrosome function and neurogenesis is revealed by the identification of many genes with centrosome-associated functions mutated in microcephaly disorders. Consistent with the major role of the centrosome in mitosis, mutations in these centrosome-related microcephaly (CRM) genes are thought to affect neurogenesis by depleting the pool of neural progenitor cells, primarily through apoptosis as a consequence of mitotic failure, or premature differentiation as a consequence of cell cycle delay and randomization of spindle orientation. However, as suggested by the wide range of microcephaly phenotypes and the multifunctional nature of many CRM proteins, this picture of CRM gene function is incomplete. Our lab is investigating CRMs using Drosophila as a model system.
CRMs and Asymmetric Division
Our lab has been interested in neural stem cell division regulation and brain development for 10 years now. We have focused on several genes critical for mitotic spindle development and centrosome function. Most prominently, we have studies the role of Abnormal Spindles (Asp) and the CRMs Pericentrin- Like-Protein (PLP).
- Micro-computed tomography as a platform for exploring Drosophila development
Schoborg TA, Smith SL, Smith LN, Morris HD, Rusan NM
Development, 176685
- Same but Different – Pleiotropy in Centrosome-Related Microcephaly.
O’Neill R, Schoborg TA, Rusan NM
Molecular Biology of the Cell, 1;29(3):241-246
- An Asp-CaM complex is required for Centrosome-Pole Cohesion and Centrosome Inheritance in Neural Stem Cells
Schoborg TA, Zajac AL, Fagerstrom CJ, Guillen RX, Rusan NM
Journal of Cell Biology, 211(5):987-98
- Live imaging of Drosophila larval neuroblasts
Lerit DA, Plevock KM, Rusan NM
Journal of Visualized Experiments. 2014 Jul 7;(89)
- PLP inhibits the activity of interphase centrosomes to ensure their proper segregation in stem cells
Lerit DA, Rusan NM.
Journal of Cell Biology. 2013 Sep 30;202(7):1013-22