Cell division ensures chromosome segregation into two daughter cells, facilitated by the spindle, a microtubule-based structure. Centrosomes at the spindle poles regulate microtubule nucleation, while chromosomes align at the center. Various proteins tightly control spindle dynamics, including plus-end and minus-end binding proteins, motor proteins, and crosslinkers. Motor proteins drive poleward flux, a conveyor-belt-like movement crucial for chromosome segregation, by sliding bridging microtubules and transmitting force to kinetochore fibers via crosslinkers.

The role of minus-end binding proteins in poleward flux regulation has been underexplored. My thesis focuses on WDR62, CAMSAP1, and kinesin-13 family proteins. I discovered that CAMSAP1 protects microtubule minus ends from MCAK-dependent depolymerization and is a precise regulator of poleward flux without affecting spindle architecture or cell division efficiency. Using CAMSAP1 as a tool, we studied correlations between poleward flux defects and the primary microcephaly induced by WDR62 mutations.

WDR62 depletion reduces flux speed, while CAMSAP1 depletion increased it; co-depletion restored normal flux speed. These rescues correct chromosomes segregation, reduces the presence of DNA damage markers, and improved cell proliferation, brain size, and cognitive function in a primary microcephaly Drosophila model.