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Florencia Cavodeassi

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fcavodeassi@cbm.uam.es
020 3549 5642 (t)
33338 (internal)

In January 2012 I moved to the CBMSO in Madrid (Spain) where I hold a Ramon y Cajal Junior Investigator Award, and where I will continue my studies on eye morphogenesis.

The optic vesicles are formed as evaginations of the forebrain, but prior to this, the group of cells that will give rise to the eyes exists as a single bilateral domain called the eye field. For this retinal primordium to give rise to the mature retina, further patterning of the eye field must be coordinated with cell proliferation and morphogenesis. Soon after the specification of the eye field during the early stages of neural plate regionalisation, extensive morphogenetic movements split this domain in two, one on each side of the midline. Each one of these domains will undergo further morphogenesis and patterning to give rise eventually to the optic vesicles (Figure 1).

Figure 1: (A) Organisation of the forebrain territories at neural plate stage. The groups of cells giving rise to each territory are shown in different colors. (B-D) The same color code is used to show the relative positions of the different territories in embryonic brains at a later stage of development, from lateral (B), dorsal (C) and ventral (D) views. Taken from Cavodeassi et al., (2009) Squire LR (ed.) Encyclopedia of Neuroscience, vol. 4, 321-325.

By making use of the zebrafish embryo as a model system, we have analysed the early steps of eye formation, and the role of a well-known signalling pathway, the Wnt pathway, during this process (Figure 2). Our work has revealed an essential role for the Wnt11 signalling molecule and its likely receptor Fz5, coordinating eye field specification and morphogenesis [Cavodeassi et al. (2005) Neuron, vol. 47, pgs 43-56]. These findings uncovered a novel link between the Wnt signalling pathway, fate determination and morphogenesis of the eye, and highlighted the importance of precisely coupling fate determination and morphogenesis during eye formation.

Figure 2: Manipulation of the Wnt pathway activity has various effects on eye formation. Dorsal views of 24hpf embryos with transplants of cells (labelled in brown) overexpressing different components of the Wnt pathway. Wnt8b overexpression interferes with eye formation (asterisk in B), while Wnt11 overexpression leads to the formation of bigger, misshapen eyes (asterisk in C). A control transplant expressing GFP does not have any effect on eye development (A). The optic vesicles are labelled by the expression of the rx2 gene (blue). Anterior is to the left.

In the last couple of years my interests have become focussed upon understanding the cellular events underlying optic vesicle evagination and maturation. My initial studies on eye morphogenesis have resulted in a recent publication [Picker, Cavodeassi et al., (2009), PLoS Biology vol. 7, e1000214] where we describe for the first time by time lapse in vivo analysis, how fate specification and morphogenesis are coordinated during maturation of the optic vesicles. In collaboration with Kenzo Ivanovitch in the lab, we are now starting to describe the earlier remodelling events that underlie the transformation of a single eye field domain into two eye vesicles. This is an extremely dynamic morphogenetic event, involving coordinated cell migration and tissue remodelling (Figure 3).

Figure 3: Frontal view of the evaginating eye field (labelled by Tg{rx3:GFP} expression, red) at 11.5hpf (A), 12.5hpf(B) and 13.5hpf (C). The apical domain of the cells is highlighted in green by immunostaining with antibodies to ZO-1 (A,B) and aPKC (C).

Defects in optic vesicle evagination and maturation can lead to congenital eye malformations such as anophthalmia, coloboma, microphthalmia and cyclopia. Therefore, these studies are not only fundamental to our understanding of the complex processes leading to the formation of a functional eye but additionally, they will allow us to gain further insight into the causes for those hereditary diseases.

In addition to this line of research, I am working in collaboration with other colleagues from the Wilson’s Lab in a number of projects focused on other aspects of eye morphogenesis and retinal differentiation that, when affected in any way, underlie various hereditary malformations, such as ocular colobomas or retinal degeneration.

A) Analysis of the cellular events leading to optic fissure closure and identification of genes and signalling pathways involved in this process. In collaboration with Gaia Gestri
We are using several approaches to analyse the behaviour of cells during optic fissure closure and the role of some candidate pathways in this morphogenetic process (find more here).

B) Coordination of cell proliferation and differentiation during retinal differentiation. In collaboration with Kara Cerveny and Kate Turner
We have made use of a zebrafish mutant, flotte lotte, where cell cycle progression is impaired. Our analysis has uncovered the importance of tightly coordinating cell cycle progression with the secretion of certain signals to control when and how terminal cell cycle exit and differentiation occur in the retina [Cerveny, Cavodeassi et al. (2010) Development, vol 137, 2107-2115]. Find more here.

C) The optic tectum as a model to study neural stem cell biology. In collaboration with Mate Varga and Kara Cerveny
We have recently started to characterise the tectal stem cell niche in the developing zebrafish. The tectal stem cell niche is very close to the surface of the brain, allowing direct observation of stem cells in the living organism. We will exploit this characteristic of the zebrafish, and the wide variety of transgenic and genetic tools available to learn more on the biology of neural stem cells (find more here).

Past support: International Postdoctoral Fellowships from the Marie Curie European Program and the HFSP; MRC Project Grant. Current support: BBSRC Project Grant; Programme Grant from the Wellcome Trust.

SELECTED PUBLICATIONS

Cavodeassi F, Ivanovitch K, Wilson SW. (2013)
Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis.
Development. 2013 Oct;140(20):4193-202.
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Ivanovitch K, Cavodeassi F, Wilson SW (2013)
Precocious Acquisition of Neuroepithelial Character in the Eye Field Underlies the Onset of Eye Morphogenesis
Developmental Cell, October 2013
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Valdivia LE, Young RM, Hawkins TA, Stickney HL, Cavodeassi F, Schwarz Q, Pullin LM, Villegas R, Moro E, Argenton F, Allende ML, Wilson SW. (2011)
Lef1-dependent Wnt/{beta}-catenin signalling drives the proliferative engine that maintains tissue homeostasis during lateral line development.
Development. 2011 Sep;138(18):3931-41
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Cerveny, K.L., Cavodeassi, F., K. J. Turner, T. A. de Jong-Curtain, J. K. Heath, and S. W. Wilson (2010)
The zebrafish flotte lotte mutant reveals that the local retinal environment promotes the differentiation of proliferating precursors emerging from their stem cell niche
Development 137: 2107-2115
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Cavodeassi, F.; Kapsimali, M.; Wilson, S.W.; Young, R. (2009 )
Forebrain: early development
In L. R. Squire (editor) Encyclopedia of Neuroscience 4:321-325. Elsevier. Oxford:Academic Press.
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Picker A, Cavodeassi F, Machate A, Bernauer S, Hans S, Abe, G., Kawakami, K., Wilson, S.W. and Brand, M. (2009)
Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina
PLoS Biol 7(10)
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Hawkins,T.A., Cavodeassi,F., Erdélyi,F., Szabó,G., Lele,Z. (2008)
The small molecule Mek1/2 inhibitor U0126 disrupts the chordamesoderm to notochord transition in zebrafish.
BMC Developmental Biology 17:42-42
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Cavodeassi, F., Carreira-Barbosa, F., Young, R.M., Concha, M.L., Allende, M.L., Houart, C., Tada, M., Wilson, S.W. (2005)
Early Stages of Zebrafish Eye Formation Require the Coordinated Activity of Wnt11, Fz5, and the Wnt/ -Catenin Pathway.
Neuron 47:43-56
click to download pdf

Cavodeassi,F., Rodriguez,I., Modolell,J. (2002)
Dpp signaling is a key effector of the wing-body wall subdivision of the Drosophila mesothorax.
Development 129: 3815-3823
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Cavodeassi,F., Modolell,J., Gomez-Skarmeta,J.L. (2001)
The Iroquios family of genes: from body building to neural patterning.
Development 128: 2847-2855
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Cavodeassi,F., Modolell,J., Campuzano,S. (2000)
The Iroquois homeobox genes function as dorsal selectors in the Drosophila head.
Development 127: 1921-1929
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Diez del Corral,R., Aroca,P., Gomez-Skarmeta,J.L., Cavodeassi,F., Modolell,J. (1999)
The Iroquois homeodomain proteins are required to specify body wall identity in Drosophila.
Genes and Development 13: 1754-1761
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Cavodeassi,F., Diez del Corral,R., Campuzano,S., Dominguez,M. (1999)
Compartments and organising boundaries in Drosophila: the role of the Iroquois homeodomain proteins.
Development 126: 4933-4942
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