Figure 1.

Scheme of the mechanism inducing tetraploid RGCs in the chick retina. (A) Retinal precursors undergo S-phase (dark gray nucleus) at the basal neuroepithelium (S-phase-1), and they displace their nuclei to the apical neuroepithelium during G2, showing 4C DNA content. Then, they undergo mitosis at the apical portion of the neuroepithelium. This division gives rise to precursors with 2C DNA content that undergo a new round of interkinetic nuclear movement (see ref.⁷⁸). Alternatively, daughter cells may undergo neuronal differentiation (gray cytoplasm). Some of the differentiating RGCs can reactivate the cell cycle (S-phase-2) in response to NGF as they migrate to the basal neuroepithelium, where the GCL will be located. In the presence of BDNF, RGCs remain with 4C DNA content (i.e. tetraploid neurons), whereas in its absence they undergo ectopic mitosis at the basal neuroepithelium and die. (B) An illustrative image showing p75^NTR-positive differentiating RGCs undergoing S-phase-2 at the apical neuroepithelium (arrows). In contrast, precursors undergoing S-phase-1 (arrowhead) are located basally. (C) An illustrative image showing an RA4-positive differentiating RGC undergoing ectopic mitosis, revealed with phosphoHistone H3 immunolabeling (pH3), at the basal neuroepithelium (arrow). In contrast, precursors undergo mitosis at the apical neuroepithelium (arrowhead). Bisb.: bisbenzimide.