Direct non-cell autonomous Pax6 activity regulates eye development in the zebrafish

A first strategy was to inject a one-cell embryo with a mRNA encoding a secreted single-chain anti-Pax6 antibody. A second, complementary, strategy was to inject a Pax6 antibody in the blastula extracellular milieu. In both cases, 'dissymmetric eyes', 'one eye only' and 'no eye' phenotypes were produced. In most cases, lens phenotypes paralleled retina malformations. Although eye phenotypes were analyzed 30 hours post-fertilization, there was a strong correlation between early eye field asymmetry, early asymmetry in Pax6 expression and later-occurring eye malformations. Several controls were introduced, demonstrating that the effect is specific to Pax6 and cannot be explained by intracellular antibody activities.This study supports the hypothesis that the Pax6 transcription factor is also a signaling molecule with direct non-cell autonomous activity.Eye formation is one of the most popular models used to study the development and evolution of sensory systems [1]. Similarities exist between vision apparatus across species, leading to the two hypotheses of convergent evolution versus monophyletic origin [2]. This system is also widely used for induction studies due to the inductive interactions that take place between neural and non-neural tissues in the course of eye development. Spemann was the first to propose that the interaction between the neural fold and the surface ectoderm is at the origin of the induction of lens formation [3-5]. This induction between the two tissues has been challenged and it has been hinted that all species may not use identical strategies to develop a visual apparatus [6-8]. Although these evolutionary and developmental issues are not fully resolved, it is now largely accepted that certain shared genetic pathways play important functions in the development of vision across species.The main breakthrough in the understanding of how the eye has evolved and develops has come from genetic analysis, in particular the identification of Pax6 as