Pathways regulating lens induction in the mouse.

Abstract

For more than a century, the lens has provided a relatively simple structure in which to study developmental mechanisms. Lens induction, where adjacent tissues signal the cell fate changes that result in lens formation, have been of particular interest. Embryological manipulations advancing our understanding have included the Spemann optic rudiment ablation experiments, optic vesicle transplantations as well as more contemporary work employing lineage tracers. All this has revealed that lens induction signaling is a multi-stage process involving multiple tissue interactions. More recently, molecular genetic techniques have been applied to an analysis of lens induction. This has led to the identification of signaling pathways required for lens induction and early lens development. These include the bone morphogenetic protein (Bmp) signaling pathways where Bmp4 and Bmp7 have been implicated. Though no fibroblast growth factor (Fgf) ligand has been implicated at present, the Fgf signaling pathway clearly has an important role. A series of transcription factors involved in early lens development have also been identified. These include Pax6, the Meis transcription factors, Six3, Mab21l1, FoxE3, Prox1 and Sox2. Importantly, analysis has indicated how these elements of the lens induction pathway are related and has defined genetic models to describe the process. It is a future challenge to test existing genetic models and to extend them to incorporate the tissue interactions mediated by the molecules involved. Given the complexity of this and many other developmental processes, a second century of analysis will be welcome.