Teleost retina : a model to study neurogenesis and angiogenesis

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.

List of scientific papers

I. Kitambi SS, Hauptmann G (2007). "The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain." Gene Expr Patterns 7(4): 521-8.
https://doi.org/10.1016/j.modgep.2006.10.006

II. Kitambi SS, Malicki JJ (2008). "Spatiotemporal features of neurogenesis in the retina of medaka, Oryzias latipes." Dev Dyn 237(12): 3870-81.
https://doi.org/10.1002/dvdy.21797

III. Kitambi SS, McCulloch K, Peterson R, Malicki J (2009). "Small molecule screen for compounds that affect vascular development in the zebrafish retina." Mechanisms of Development. [Accepted]
https://doi.org/10.1016/j.mod.2009.01.002

IV. Kitambi SS, Archer A, Hallgren SL, Olsen HK, Gustafsson JÅ, Mode A (2009). "The role of liver X receptor (lxr) in the developing eye." [Manuscript]