Zebrafish Research at UCL

Mate Varga

Post Doc
m.varga@ucl.ac.uk
00 44 (0)20 7679 2928 (t)
00 44 (0)20 7679 7349 (f)
32928 (internal)

I have recently moved from UCL and my cv is below for reference only.

Undergraduate
Faculty of Science, Eötvös Loránd University, Budapest, Hungary
Majors: Biology / Molecular Biology - Genetics
Tutor: Dr. Ferenc Olasz
1996-2001

Graduate
Department of Biology, University of Pennsylvania, Philadelphia, USA
PhD in Cell and Molecular Biology
PI: Dr. Eric Weinberg
2001-2006

During my PhD my main goal was to uncover some early aspects of the vertebrate dorso-ventral (DV) and anteroposterior (AP) patterning. Using the maternal recessive mutation ichabod, I studied the roles of the two zebrafish ß-catenin genes in the formation of the organizer, and also how much AP patterning can still occur in the complete absence of early dorsal structures.

In Steve's lab my main interest is to study the role of the gene stem-cell leukemia (scl/tal1) during the development of the zebrafish brain. As its name would suggest, Scl is a critical factor during haematopoiesis, originally discovered for its role in T-cell acute lymphocytic leukemia. During earlier stages of development scl is expressed in haematopoietic and endothelial precursors, however during later stages it also becomes robustly expressed in specific domains of the zebrafish central nervous system (CNS). Given its prominent role during blood- and vasculature formation, it is likely that Scl has also functions in neurogenesis, and we hope that our work will help to shed light on these.

Adult stem cells have fundamental importance in the regeneration and/or growth of animal bodies during post-embryonic stages. We can find such cells in our intestines, skin, bone marrow and in the male testes, and in some regions of the central nervous system (CNS).

Tectum Development
Adult neural stem cells are scarce in humans (and mammals in general), but other vertebrates - birds, reptiles, amphibians and fish - contain several populations of continuously proliferating cells in their brain, which could be used as models to study post-embryonic neurogenesis. Indeed, neurogenesis has been extensively studied in the adults of several teleost fish species and previous research has described multiple neurogenic proliferating cell populations in the anterior CNS. An interesting cell population can be found in the optic tectum (OT) of these animals, as previous BrdU and [3H]thymidine incorporation experiments both in zebrafish (Danio rerio), medaka (Oryzias latipes) and goldfish (Carassius auratus) have shown the presence of proliferating cells in the lateral, medial and caudal margins of the OT (Fig 1.)

Figure 1: Proliferative cells are present in the lateral, medial and caudal margins of the OT, as marked by BrdU uptake (A), and the expression of the cell cycle marker ccnD1 (B). (A: dorsal view; B: cross section)

The OT is one of the most important processing centers of sensory (mainly visual) information in teleost fish. Its size and complexity varies dependent on the behaviour and ecological niche of the species. During embryonic development the OT develops from the simple neuroepithelium of the mesencephalic alar plate into a complex, multilayered structure (Fig 2.), receiving and integrating inputs not only from the eyes, but also from the lateral line, telencephalon and the tori.

In a typical adult teleost tectum, such as the one of the goldfish, morphologically we can distinguish at least 11 to 15 different cell types. As the teleost OT grows during the whole lifetime of the fish, these different cell types have to be continuously generated, making the tectum an ideal model to study the biology of neural stem cells.

Figure 2: The OT develops from the neuroepithelium of the mesencephalic alar plate (green) (A) into a complex, multilayered organ (B) which contains several morphologically distinct neuronal populations. Using nuclear stains (blue) and antibodies against acetylated-tubulin (red) and GFP (green), the main layers of the adult tectum were visualized in a transgenic fish line (C). (SM = stratum marginale, SO = startum opticum, SGC = stratum grisea centrale, SPV = stratum periventriculare). Despite decades of intensive research into the development of retinotectal axons and the formation of topographic retinotectal maps, our understanding of the molecular cues that drive the embryonic and post-embryonic development of the tectum is scant. Previous evidence suggests that ingrowing retinal fibers can have an effect on the proliferation of precursor cells in the tectum, but we have no information about the molecules that relay this effect. Similarly our knowledge is very limited about the signaling mechanisms that ensure the development of the 12+ cell types from a single pluripotent progenitor in the OT.

For all these reasons, we choose to study the development of the teleost optic tectum, trying to unswer some key questions: how can complicated, multilayered structures arise from a small set of pluripotent cells? What is the identity of the neural stem cells and what regulates their maintenance? We are using a combination of forward and reverse genetics, and sophisticated high-resolution imaging to try to answer these questions.

SELECTED PUBLICATIONS

Cerveny KL, Varga M, Wilson SW. (2012)
Continued growth and circuit building in the anamniote visual system.
Dev Neurobiol. 2012 Mar;72(3):328-45.

Varga M, Maegawa S, Bellipanni G, Weinberg ES (2007)
Chordin Expression, Mediated by Nodal and FGF Signaling, is Restricted by Redundant Function of Two ß-catenins in the Zebrafish Embryo
Mech. Dev. 124: 775-791

Maegawa S, Varga M, Weinberg ES (2006 )
FGF signaling is required for ß-catenin-mediated induction of the zebrafish organizer.
Development 133: 3265-3276

Bellipanni G, Varga M, Maegawa S, Imai Y, Kelly C, Myers AP, Chu F, Talbot WS, Weinberg ES. (first co-author) (2006)
Essential and opposing roles of zebrafish ß-catenins in the formation of dorsal axial structures and neurectoderm.
Development 133: 1299-1309