The demonstration that embryonic stem cell (ESC) cultures could self-organise into optic cup-like structures provided a striking and elegant example of the degree to which tissues and organs can self-organise. But outside the embryo context, and in the absence of more global patterning cues, can they adopt appropriate axial identity and polarity? Mototsugu Eiraku and co-workers now investigate dorsoventral (DV) patterning in in vitro formed, mouse ESC-derived optic cups (p. 3895). In vivo, DV polarity is regulated by the Wnt, Shh and BMP pathways, leading to dorsal-specific expression of Tbx5 and ventral expression of Vax2. The authors find that these expression domains, and the asymmetric morphogenetic events that form the optic fissure, are largely preserved in ESC-derived optic cups, although less robustly than in vivo. Ventral identity seems to be the default status, with dorsal identity being induced by localised activation of BMP signalling. As in vivo, this is controlled by Wnt signalling, which appears to be induced specifically at the retinal/non-retinal border at one side of the forming optic cup. How this local activation of Wnt is achieved in the in vitro system is unclear, but the data presented highlight the impressive degree to which tissues can self-organise, and demonstrate the utility of this in vitro system for understanding both patterning and morphogenesis.
