Homophilic interaction of cell adhesion molecule 3 coordinates retina neuroepithelial cell proliferation

Abstract

Correct cell number generation is central to tissue development. However, in vivo roles of coordinated proliferation of individual neural progenitors in regulating cell numbers of developing neural tissues and the underlying molecular mechanism remain mostly elusive. Here, we showed that wild-type (WT) donor retinal progenitor cells (RPCs) generated significantly expanded clones in host retinae with G1-lengthening by p15 (cdkn2a/b) overexpression (p15+) in zebrafish. Further analysis showed that cell adhesion molecule 3 (cadm3) was reduced in p15+ host retinae, and overexpression of either full-length or ectodomains of Cadm3 in p15+ host retinae markedly suppressed the clonal expansion of WT donor RPCs. Notably, WT donor RPCs in retinae with cadm3 disruption recapitulated expanded clones that were found in p15+ retinae. More strikingly, overexpression of Cadm3 without extracellular ig1 domain in RPCs resulted in expanded clones and increased retinal total cell number. Thus, homophilic interaction of Cadm3 provides an intercellular mechanism underlying coordinated cell proliferation to ensure cell number homeostasis of the developing neuroepithelia.

Necl-1/CADM3 regulates cone synapse formation in the mouse retina

“…A recent study showed that Cadm3-mediated homophilic interaction provides an intercellular mechanism underlying coordinated cell proliferation and ensures cell number homeostasis of developing neuroepithelia in zebrafish retina. 46 In mouse retina, Cadm-3-mediated homophilic interaction may also be important in cell proliferation at the early proliferative stage. This evidence supports the symmetric distribution of Necl-1 observed in Necl-1 spots.…”