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Teleost retina: a model for study neurogenesis and angiogenesis
Södertörn University, School of Life Sciences. Karolinska Institutet.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Stockholm: Karolinska instiutet , 2009. , 37 p.
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:sh:diva-31551ISBN: 978-91-7409-365-0 (print)OAI: oai:DiVA.org:sh-31551DiVA: diva2:1060747
Public defence
2009-03-30, Månen, Alfred Nobels allé 8, Huddinge, 09:00
Opponent
Supervisors
Available from: 2016-12-29 Created: 2016-12-29 Last updated: 2016-12-29Bibliographically approved
List of papers
1. The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain
Open this publication in new window or tab >>The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain
2007 (English)In: Gene Expression Patterns, ISSN 1567-133X, E-ISSN 1872-7298, Vol. 7, no 4, 521-528 p.Article in journal (Refereed) Published
Abstract [en]

Mammalian Nr2e1 (Tailless, Mtll or Tlx) and Nr2e3 (photoreceptor-specific nuclear receptor, Pnr) are highly related orphan nuclear receptors, that are expressed in eye and forebrain-derived structures. In this study, we analyzed the developmental expression patterns of zebrafish nr2e1 and nr2e3. RT-PCR analysis showed that nr2e1 and nr2e3 are both expressed during embryonic and post-embryonic development. To examine the spatial distribution of nr2e1 and nr2e3 during development whole-mount in situ hybridization was performed. At tailbud stage, initial nr2e1 expression was localized to the rostral brain rudiment anterior to pax2.1 and eng2 expression at the prospective midbrain-hindbrain boundary. During Subsequent stages, nr2e1 became widely expressed in fore- and midbrain primordia, eye and olfactory placodes. At 24 hpf, strong nr2e1 expression was detected in telencephalon, hypothalamus, dorsal thalamus, pretectum, midbrain tectum, and retina. At 2 dpf, the initially widespread nr2e1 expression became more restricted to distinct regions within the fore- and midbrain and to the retinal ciliary margin, the germinal zone which gives rise to retina and presumptive iris. Express on of nr2e3 was exclusively found in the developing retina and epiphysis. In both structures, nr2e3 expression was found in photoreceptor cells. The developmental expression profile of zebrafish nr2e1 and nr2e3 is consistent with evolutionary conserved functions in eye and rostral brain structures.

National Category
Developmental Biology Genetics
Identifiers
urn:nbn:se:sh:diva-14236 (URN)10.1016/j.modgep.2006.10.006 (DOI)000244570400018 ()17127102 (PubMedID)2-s2.0-33846590514 (Scopus ID)
Available from: 2011-12-19 Created: 2011-12-19 Last updated: 2016-12-29Bibliographically approved
2. Spatiotemporal Features of Neurogenesis in the Retina of Medaka, Oryzias latipes
Open this publication in new window or tab >>Spatiotemporal Features of Neurogenesis in the Retina of Medaka, Oryzias latipes
2008 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 237, no 12, 3870-3881 p.Article in journal (Refereed) Published
Abstract [en]

The vertebrate retina is very well conserved in evolution. Its structure and functional features are very similar in phyla as different as primates and teleost fish. Here, we describe the spatiotemporal characteristics of neurogenesis in the retina of a teleost, medaka, and compare them with other species, primarily the zebrafish. Several intriguing differences are observed between medaka and zebrafish. For example, photoreceptor differentiation in the medaka retina starts independently in two different areas, and at more advanced stages of differentiation, medaka and zebrafish retinae display obviously different patterns of the photoreceptor cell mosaic. Medaka and zebrafish evolutionary lineages are thought to have separated from each other 110 million years ago, and so the differences between these species are not unexpected, and may be exploited to gain insight into the architecture of developmental pathways. Importantly, this work highlights the benefits of using multiple teleost models in parallel to understand a developmental process.

National Category
Developmental Biology
Identifiers
urn:nbn:se:sh:diva-14114 (URN)10.1002/dvdy.21797 (DOI)000261679300038 ()2-s2.0-57149095268 (Scopus ID)
Available from: 2011-12-19 Created: 2011-12-16 Last updated: 2016-12-29Bibliographically approved
3. Small molecule screen for compounds that affect vascular development in the zebrafish retina
Open this publication in new window or tab >>Small molecule screen for compounds that affect vascular development in the zebrafish retina
2009 (English)In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 126, no 5-6, 464-477 p.Article in journal (Refereed) Published
Abstract [en]

Blood vessel formation in the vertebrate eye is a precisely regulated process. in the human retina, both an excess and a deficiency of blood vessels may lead to a loss of vision. To gain insight into the molecular basis of vessel formation in the vertebrate retina and to develop pharmacological means of manipulating this process in a living organism, we further characterized the embryonic zebrafish eye vasculature, and performed a small molecule screen for compounds that affect blood vessel morphogenesis. The screening of approximately 2000 compounds revealed four small molecules that at specific concentrations affect retinal vessel morphology but do not produce obvious changes in trunk vessels, or in the neuronal architecture of the retina. Of these, two induce a pronounced widening of vessel diameter without a substantial loss of vessel number, one compound produces a loss of retinal blood vessels accompanied by a mild increase of their diameter, and finally one other generates a severe loss of retinal vessels. This work demonstrates the utility of zebrafish as a screening tool for small molecules that affect eye vasculature and presents several compounds of potential therapeutic importance.

National Category
Developmental Biology
Identifiers
urn:nbn:se:sh:diva-13901 (URN)10.1016/j.mod.2009.01.002 (DOI)000266975100016 ()19445054 (PubMedID)2-s2.0-67349147007 (Scopus ID)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2017-07-18Bibliographically approved
4. The role of liver X receptor (lxr) in the developing eye
Open this publication in new window or tab >>The role of liver X receptor (lxr) in the developing eye
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-8459 (URN)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2011-05-12 Created: 2011-05-12 Last updated: 2016-12-29Bibliographically approved

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