Msps governs acentrosomal microtubule assembly and reactivation of quiescent neural stem cells

The ability of stem cells to switch between quiescence and proliferation is crucial for tissue homeostasis and regeneration. Drosophila quiescent neural stem cells (NSCs) extend a primary cellular protrusion from the cell body prior to their reactivation. However, the structure and function of this protrusion are not well established. Here, we show that in the protrusion of quiescent NSCs, microtubules are predominantly acentrosomal and oriented plus‐end‐out toward the tip of the primary protrusion. We have identified Mini Spindles (Msps)/XMAP215 as a key microtubule regulator in quiescent NSCs that governs NSC reactivation via regulating acentrosomal microtubule growth and orientation. We show that quiescent NSCs form membrane contact with the neuropil and E‐cadherin, a cell adhesion molecule, localizes to these NSC‐neuropil junctions. Msps and a plus‐end directed motor protein Kinesin‐2 promote NSC cell cycle re‐entry and target E‐cadherin to NSC‐neuropil contact during NSC reactivation. Together, this work establishes acentrosomal microtubule organization in the primary protrusion of quiescent NSCs and the Msps‐Kinesin‐2 pathway that governs NSC reactivation, in part, by targeting E‐cad to NSC‐neuropil contact sites. SYNOPSIS In the primary protrusion of quiescent neural stem cells (NSCs), microtubules are predominantly acentrosomal and oriented plus‐end‐out. Msps/XMAP215 and Kinesin‐2 promote NSC cell cycle re‐entry and target E‐cadherin to NSC‐neuropil contact during NSC reactivation. In the primary protrusion of quiescent NSCs, microtubules are predominantly acentrosomal and oriented plus‐end‐out. Mini Spindles (Msps)/XMAP215 is a key regulator of acentrosomal microtubule growth and orientation in the primary protrusion of quiescent NSCs. Quiescent NSCs form membrane contact with the neuropil and E‐cadherin, a cell adhesion molecule, localizes to these NSC‐neuropil junctions. Msps and a plus‐end directed motor protein Kinesin‐2 promote NSC cell cycle re‐entry and target E‐cadherin to NSC‐neuropil contact during NSC reactivation. Graphical Abstract The microtubule regulator Mini Spindles (Msps)/XMAP215 promotes Drosophila neural stem cell activation, by targeting adhesion molecule E‐cadherin via Kinesin‐2 motors to neural stem cell‐neuropil contact sites.