The <i>Pax6</i> master control gene initiates spontaneous retinal development via a self-organising Turing network

Abstract

Understanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a 'master control gene' called <i>Pax6</i>, which is both necessary and sufficient for eye development. Yet precisely how <i>Pax6</i> achieves this deeply homologous function is poorly understood. Using the chick as a model organism, we show that vertebrate <i>Pax6</i> interacts with a pair of morphogen-coding genes, <i>Tgfb2</i> and <i>Fst</i>, to form a putative Turing network, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the first organisational axis of the eye and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independently of the highly ordered tissue interactions that help to assemble the eye <i>in vivo</i> These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cups <i>in vitro</i> We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies.