Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS

The bipotential Ganglion Mother Cells, or GMCs, in the Drosophila CNS asymm etrically divide to generate two distinct post-mitotic neurons. Here, we sh ow that the midline repellent Slit (Sli), via its receptor Roundabout (Robo ), promotes the terminal asymmetric division of GMCs. In GMC-1 of the RP2/s ib lineage, Slit promotes asymmetric division by down regulating two POU pr oteins, Nubbin and Mitimere. The down regulation of these proteins allows t he asymmetric localization of Inscuteable, leading to the asymmetric divisi on of GMC-1. Consistent with this, over-expression of these POU genes in a late GMC-1 causes mis-localization of Inse and symmetric division of GMC-1 to generate two RP2s. Similarly, increasing the dosage of the two POU genes in sli mutant background enhances the penetrance of the RP2 lineage defect s whereas reducing the dosage of the two genes reduces the penetrance of th e phenotype. These results tie a cell-non-autonomous signaling pathway to t he asymmetric division of precursor cells during neurogenesis.