Hedgehog signaling is well documented to be crucial for retinal development in many organisms including Danio
rerio. Severe diseases of the visual system, such as holoprosencephaly, colobomatous microphthalmia, or cancer
are often a consequence of defects in Hedgehog signaling. However, our picture of the complex interactions
ensuring proper processing of the vertebrate visual system is still fragmentary. The aim of the presented project is
to take advantage of the wide range of tools available in the zebrafish system, to dissect and analyze the various
functions of Hedgehog signaling in eye development. Using pharmacological inhibitors of the Hedgehog pathway,
I plan to segregate the diverse roles of Hedgehog at different stages of eye development, such as the early function
in the specification of the eye`s dorsoventral axis, and a later role in directing retinal neuron differentiation. Next, I
intend to use mosaic expression of gene constructs either constitutively activating or blocking the pathway, to study
the cellular response to Hedgehog signaling, and to test the directness of the response to the signal. Live imaging
on embryos, in which Hedgehog signaling has either been blocked, or ectopically activated, will be used to learn
about the effects of Hedgehog signaling on proliferation, cell migration and lamination of the retina. Moreover, I
plan to characterize novel mutants, recently isolated by the Neumann group, and address the question whether these
mutations affect functions upstream or downstream of Hedgehog.