Asymmetric cell division (ACD) is a conserved and fundamental process in neurogenesis for generating cellular diversity across both invertebrates and vertebrates. As the principal neural stem cells (NSCs), radial glia progenitors (RGP) undergo ACD to generate self-renewing and differentiating daughter cells in the developing central nervous system. Until now, the cellular and molecular mechanisms of ACD and subsequent daughter fate choice is not well understood in vertebrates.
By using zebrafish, we have identified that the cortical polarity regulator Partitioning defective protein-3 (Par-3) plays a crucial role in the establishment of ACD through localizing the ubiquitin E3 ligase Mindbomb (Mib), which activates Notch by ubiquitinating the Notch ligand unequally in the apical daughter. Using immunocytochemistry, in vivo imaging, and other molecular genetic and biochemical methods, we are elucidating the nature of Mib asymmetry and the underlying mechanisms that orchestrate such asymmetry.