Corneal Lens Formation
Molecular Control of Lens Development
At first glance, the eye of a fruit fly (Drosophila melanogaster) and a human are very different. However, increasing evidence indicates that many conserved mechanisms are used for specifying the eye field and for generating different neuronal cell populations in the retina. However, whether molecular pathways used for generating the focusing structures of the eye – the lens and cornea – are conserved throughout evolution remains unclear. Indeed, while some progress has been made in understanding how these structures form in mammalian systems, little to nothing is known regarding how they form in invertebrates such as flies.
Thus, one question in our lab is aimed at understanding how the corneal lens forms in Drosophila and testing the hypothesis that these processes are similar to those used in humans. If true, this would allow us to take advantage of the powerful genetics available in Drosophila to better understand human lens development and to create helpful therapies for patients suffering from cataracts and other cornea / lens-associated diseases.
Genesis of the corneal lens in Drosophila occurs during the latest larval stages, just prior to pupation. Initially, a group of cells known as the “R7 equivalence group” have the potential to become either a photoreceptor neuron (the R7) or a lens-secreting cell (cone cell, CC). This retina vs. lens fate decision requires input from two primary signaling pathways: Ras and Notch. Our recent studies have found that two direct downstream targets of these signaling pathways, the transcription factors Prospero (Pros) and dPax2, function antagonistically during R7 vs. CC differentiation, but act synergistically to promote lens formation.
Importantly, vertebrate factors related to Pros and dPax2, known as Prox1 and Pax6, are also important for lens development in mice and humans, supporting the hypothesis that lens formation in vertebrates and invertebrates use evolutionarily conserved pathways. Likewise, Prox1 and vertebrate Pax2 and Pax6 are important regulators for many aspects of nervous system development. Therefore, our studies on understanding the fundamental mechanisms underlying Pros and dPax2 function during fly eye development should provide a useful platform for developing better treatments for human eye and brain diseases.
