Neural Cell Adhesion Molecule Ncam1b Promotes Effective Hair Cell Regeneration in Zebrafish Neuromasts

This study examines the distinct roles of the neural cell adhesion molecules Ncam1a and Ncam1b in zebrafish neuromasts during both homeostasis and hair cell regeneration. While both molecules contribute to the initial development of the lateral line system, previous work showed that a morpholino knockdown of ncam1b causes more severe developmental defects than ncam1a knockdown. However, in ncam1b mutants, only minor changes in FGF/Wnt signaling and cell proliferation are observed in the migrating primordium, which do not affect overall development of the lateral line development, suggesting compensation by Ncam1a. This work shows that after neomycin-induced hair cell loss, only Ncam1b is strongly re-expressed in regenerating hair and support cells. ncam1b mutants show delayed hair cell regeneration, with an increased number of proliferating support cells but impaired differentiation into hair cells. Notably, Ncam1a is not re-expressed during regeneration in ncam1b mutants. These regeneration defects likely arise from disrupted interactions of signaling pathways. Our data suggest that Ncam1b supports regeneration by sustaining the FGF pathway activity required for atoh1a induction. It also maintains balanced Notch signaling, which regulates support cell fate decisions. Together, these results highlight the crucial, non-redundant role of Ncam1b in coordinating signaling pathways to ensure proper hair cell regeneration in zebrafish neuromasts.