Zhao X1,2 Choi R1,2 Dong Z1, Guo S1*
2Co-first author
*Corresponding author
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.