In many systems, stem cell fate is regulated by Notch signalling. One such example is the Drosophila midgut, where intestinal stem cells (ISCs) can divide either asymmetrically, generating a Notch-positive enteroblast (EB) and a Notch-negative ISC, or symmetrically, either forming two EBs or two ISCs. But what determines the outcome of ISC division, and how does Notch signalling influence this? Joaquín de Navascués, Jordi Garcia-Ojalvo and co-workers address this question on p. 1177 using a combination of experimental and modelling approaches. Their key insight is that contact area between the two daughter cells correlates with cell fate: where the contact area is small, both cells tend to remain ISCs, where it is larger, one or both cells differentiate. Since Delta-Notch signalling involves direct contact between the two cells, the area of contact can influence the effective signalling threshold. Both the computational and experimental analyses support the idea that the pattern of cell fates following ISC division can be at least partly explained by variability in cell contact area, and hence in the levels of Notch-Delta signalling between the two daughter cells. That such a model might also apply in other stem cell systems is an intriguing possibility.
