Mad dephosphorylation at the nuclear pore is essential for asymmetric stem cell division

Significance Stem cells often divide into two different cell types: stem cells and differentiating cells. This phenomenon, called “asymmetric cell division,” is important for balancing the number of these two cell populations. Here, we demonstrate that phosphorylated Mad (pMad), the immediate downstream molecule of the niche signal, is asymmetrically partitioned within a dividing stem cell before the completion of cytokinesis. We identified a known Mad phosphatase, Dullard, as an essential factor for this process. Mathematical modeling recapitulates high sensitivity of the ratio of pMad levels to the Mad phosphatase activity and explains how the early asymmetry arises in a shared cytoplasm.