Biovetenskaper och näringslära / Biosciences and Nutrition
Doi
Abstract
Teleost models, zebrafish and medaka have become popular models to study
various aspects of developmental biology and genetics. The rapid
embryonic development, transparent embryos and the availability of many
mutants for various developmental and molecular pathways contribute to
the usefulness of these models. The availability of various biochemical,
molecular and genetic techniques applicable on these models facilitate in
dissecting developmental processes.
Teleost retina shows very high similarity to that seen in mammalian
retina. The arrangement of the six types of neurons and one type of glia
is very similar. Zebrafish has been extensively used in gaining insight
into the development and functioning of the retina. Medaka, on the other
hand has not been so extensively capitalized as zebrafish. The current
study characterizes expression of genes mainly from the nuclear receptor
family and establishes the role of zebrafish liver x receptor in
governing the size, patterning and neurogenesis of the retina in
zebrafish. We also establish the time line of the retinal patterning of
medaka retina. Zebrafish and medaka retina show both similarity and
difference in the developmental events governing the patterning of the
retina. In zebrafish, retinal neurogenesis follows a fan gradient pattern
starting at the ventro-nasal region. In medaka, neurogenesis starts from
the central retina. An additional, second domain of neurogenesis is seen
with the patterning of photoreceptors in medaka. This observation
highlights the possibility of utilizing these two species as comparative
models in gaining rapid understanding of retinal development and
function.
This study also establishes the time line of vascular development in the
zebrafish retina, an important event required for normal function.
Similar to neurogenesis, vasculaturedevelops rapidly and this feature was
utilized to develop a small molecule-screening assay. The screening
resulted in identification of five compounds that produced phenotype
ranging from decrease in the number of vessels to loss of vessels
specifically in the retina. To gain insight into the mode of action,
further analyses of three of the five identified compounds, using either
morpholino knockdown or structural similarity search was done. This study
highlights the advantage of using zebrafish model to perform medically
relevant chemical screen
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