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.

中文翻译：

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细胞粘附分子3的同亲相互作用协调视网膜神经上皮细胞增殖

正确的细胞数量生成对于组织发育至关重要。然而，个体神经祖细胞协调增殖在调节发育神经组织细胞数量的体内作用以及潜在的分子机制仍然大多难以捉摸。在这里，我们发现野生型（WT）供体视网膜祖细胞（RPC）在宿主视网膜中产生显着扩增的克隆，并通过斑马鱼中的 p15（cdkn2a/b）过表达（p15+）实现 G1 延长。进一步分析表明，p15+宿主视网膜中细胞粘附分子3（cadm3）减少，并且p15+宿主视网膜中Cadm3全长或胞外域的过度表达显着抑制WT供体RPC的克隆扩增。值得注意的是，具有 cadm3 破坏的视网膜中的 WT 供体 RPC 重现了在 p15+ 视网膜中发现的扩展克隆。更引人注目的是，RPC 中无胞外 ig1 结构域的 Cadm3 过表达导致克隆扩大和视网膜总细胞数增加。因此，Cadm3 的同源相互作用提供了协调细胞增殖的细胞间机制，以确保发育中的神经上皮的细胞数量稳态。