Endocytosis by Numb breaks Notch symmetry at cytokinesis

Abstract

Cell-fate diversity can be generated by the unequal segregation of the Notch regulator Numb at mitosis in both vertebrates and invertebrates. Whereas the mechanisms underlying unequal inheritance of Numb are understood, how Numb antagonizes Notch has remained unsolved. Live imaging of Notch in sensory organ precursor cells revealed that nuclear Notch is detected at cytokinesis in the daughter cell that does not inherit Numb. Numb and Sanpodo act together to regulate Notch trafficking and establish directional Notch signalling at cytokinesis. We propose that unequal segregation of Numb results in increased endocytosis in one daughter cell, hence asymmetry of Notch at the cytokinetic furrow, directional signalling and binary fate choice. Asymmetric Notch signalling is important in many developmental contexts, including the division of fly sensory organ precursor (SOP) cells. Here, Notch is inactivated by Numb in the resulting pIIb daughter cell while remaining active in pIIa to direct cell fate. Using live imaging, Schweisguth and colleagues reveal that Numb and Sanpodo act together, modulating Notch trafficking to deplete it on the pIIb side of the SOP cytokinetic furrow.

Cite this article

Couturier, L., Vodovar, N. & Schweisguth, F. Endocytosis by Numb breaks Notch symmetry at cytokinesis. Nat Cell Biol 14, 131–139 (2012). https://doi.org/10.1038/ncb2419

View full text

>> Full Text:   Endocytosis by Numb breaks Notch symmetry at cytokinesis