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.