Roles of different Delta ligands in intercellular information relay for the segmentation clock

Determine how the Notch Delta ligands with distinct properties, specifically DeltaC and DeltaD in the zebrafish segmentation clock, contribute to relaying oscillatory state information among neighboring cells to achieve synchronization of the collective rhythm.

Background

The zebrafish segmentation clock is a collective genetic oscillation that patterns the vertebrate body axis. Notch signaling couples neighboring cellular oscillators, and Delta ligands are central to this coupling: DeltaC exhibits oscillatory expression regulated by Her proteins, while DeltaD is largely non-oscillatory but its loss produces desynchronization-like phenotypes similar to core coupling components.

This paper proposes and analyzes two mechanistic hypotheses for intercellular coupling—Notch activation via Delta dimers versus Delta monomers—and shows that both can explain key phenotypes, assigning distinct roles to DeltaD (binding partner versus baseline signal). Despite these advances, it remains unresolved how different Delta ligands with distinct properties contribute to information transfer among cells, motivating targeted experiments to discriminate between the proposed mechanisms.