Each organ in the body assumes a specific shape during development, and assuming the correct shape is critical for organ function. The research proposed here examines this complex process using the vertebrate eye as a model system. Establishment of an appropriate shape during development is critical to function of the eye, and developmental deviations that cause in changes in form result in structural eye defects in humans and visual impairments. While many genes that underlie these defects have been identified, much less is known about how genetic variation results in changes to cellular behaviors that lead to these structural defects. This proposal uses the blind Mexican cavefish Astyanax mexicanus as a model system to examine the genetic and cellular basis of naturally occurring deviations in eye morphogenesis. A. mexicanus exists in two forms, a sighted, surface-dwelling form and a blind, cave-dwelling form that initially develops small eyes that subsequently degenerate. Cavefish eyes display differences in shape during development compared to surface fish, allowing for the examination of the cellular mechanisms that underlie these differences. Further, cavefish brains are significantly different from surface fish brains, providing an opportunity to investigate the relationship between the developing eye and the developing brain. How the eye assumes its proper shape, how this affects the structure of the brain, and the impact of natural genetic variants, at a cellular level, on these processes will be examined utilizing gene editing and transgenesis techniques, combined with live-imaging and an established brain atlas. Further, because the process of eye morphogenesis is highly conserved between species, these studies may further our understanding how structural eye defects in humans occur.
Assumption of a particular shape during organ morphogenesis is critical for human health, and many congenital disorders manifest as changes in form. Understanding how natural genetic variants alter cellular behaviors during development is critical to understanding organ morphogenesis and how deviations to this process that lead to human disorders occur. This proposal will examine the genes and cellular mechanisms that underlie early eye development and the relationship between the developing eye and the brain to determine how a complex organ, the eye, establishes its form and how this process affects development of the brain.
