The invariant lineage of C. elegans led to an early assumption that cell fate decisions are largely made cell-autonomously. However, it has subsequently become clear that inductive interactions between cells are essential for fate determination in this system. Moreover, these inductive interactions can be highly complex. The 8-cell stage blastomere, MS, gives rise to a number of body wall muscles. Their appropriate differentiation relies first upon an inhibitory signal from the ABp lineage at early stages, and subsequently upon an activating interaction from the ABa lineage a couple of cell cycles later. It has long been known that the activating interaction depends on Notch activity, but the nature of the signals, and the reason for this complex mechanism of cell fate determination, have remained unclear. Rueyling Lin and colleagues now identify zygotic MOM-2 (a Wnt ligand) as the Notch-dependent signal responsible for both the inhibitory and activating interaction (p. 419). Moreover, they provide evidence that this two-step mechanism is important because early inhibition is required to prevent precocious lineage restriction during this rapid phase of development. These data highlight the complex intercellular interactions, and the robust mechanisms, underlying cell fate determination in even a seemingly simple embryo like that of the worm.
