My main research and scientific interests are focused on the developmental biology of eye formation. In particular, I am fascinated by the mechanisms that transform the anterior neural ectoderm into an optic vesicle and then into a differentiated eye. During my PhD in Giuseppina Barsacchi’s laboratory (University of Pisa, Italy), I took advantage of Xenopus laevis as an experimental system to investigate the role of genes involved in the early eye field specification. Our results elucidated some of the pathways and mechanisms involved in eye specification. Specifically, we showed that the combined expression of seven transcription factors is sufficient to induce an ectopic eye in a region that, under normal conditions, is incompetent to generate neural tissue. Among these factors, we studied the function of Xsix3 and Xrx1 in detail. Our basic research contributed to the understanding of the aetiology of human patients suffering from impaired eye formation and vision as a result of six3 and chx10 haplo-insufficiency.
Eye specification is the first of many events important for eye development. One of the last events required for the formation of an eye is closure of the choroid fissure. The choroid fissure is a transient opening on the ventral side of the optic cup through which blood vessels enter and retinal axons leave the developing eye (see figure below). If the choroid fissure fails to close, then a condition termed coloboma results. Although colobomas are one of the most common hereditary eye malformations, their genetic bases and cellular aetiology remain elusive.
As a Postdoctoral Research Fellow (Telethon fellowship and Wellcome Trust funding) in Steve Wilson's laboratory in London, I’m using the zebrafish as a model system to focus on the morphogenesis of the choroid fissure to identify the genes and cell biological events that regulate this process.
Below is a cartoon showing the closure of the choroid fissure. (yellow: lens; maroon: neural retina; green: periocular mesenchymal cells; blue: retinal pigmented epithelium and optic stalk; black: extracellular space)
To address how the choroid fissure closes, I am investigating the following questions:
1) What are the main steps of choroid fissure closure? Is there similarity between this process and other epithelial fusions (e.g., dorsal closure in Drosophila and wound healing)?
2) Is the choroid fissure fusion a real fusion or just a zippering?
3) What is the polarity of the cells that mediate fusion? Is this an example of apical or basal surfaces fusing?
4) What is the role of the neural crest in regulating the morphogenesis of the eye and choroid fissure closure?
5) Which genes encode proteins that participate directly in choroid fissure closure? Which signalling pathways regulate this process?
For these studies, I am collaborating with Guiseppe Lupo, Brian Link and Nicky Ragge.
Lupo G, Gestri G, O'Brien M, Denton RM, Chandraratna RA, Ley SV,
Harris WA, Wilson SW. (2011)
Retinoic acid receptor signaling regulates choroid fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme
Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C (2010)
Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction
Markus Tschopp, Masanari Takamiya, Kara L. Cerveny, Gaia Gestri, Oliver Biehlmaier, Stephen W. Wilson, Uwe Strähle, Stephan C. F. Neuhauss (2010)
Funduscopy in Adult Zebrafish and Its Application to Isolate Mutant Strains with Ocular Defects
Gestri G, Osborne RJ, Wyatt AW, Gerrelli D, Gribble S, Stewart H,
Fryer A, Bunyan DJ, Prescott K, Collin JR, Fitzgerald T, Robinson D,
Carter NP, Wilson SW, Ragge NK. (2009)
Reduced TFAP2A function causes variable optic fissure closure and retinal defects and sensitizes eye development to mutations in other morphogenetic regulators.
Zuber M.E., Gestri G., Viczian A.S., Barsacchi G., Harris W.A. (2003)
Specification of the vertebrate eye field is regulated by a hierarchy of transcription factors expressed in the anterior neural plate.