Figure 7. Model for Rbc3a and V0a1 functions in NC cells.

(A) Rbc3a promotes association of a specific v0a1 isoform to early endosomes. In the absence of Rbc3a, endosomes acidify, but do not mature. (B) Rbc3a controls maturation of early endosomes (EE) containing Fz-Wnt complexes to contribute to multivesicular bodies (MVBs), which promote canonical Wnt signaling and EMT. In the absence of Rbc3a (or v0a1), canonical Wnt signaling decreases early (∼11 hpf) and increases later (∼20 hpf). Defects in EE maturation disrupt Fz-Wnt recycling and degradation, producing high levels of Fz-Wnt complexes at the cell membrane and aberrantly high levels of canonical Wnt signaling, which drives NC cells to a pigment progenitor fate.