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III
ABSTRACT
Serotonin (5-HT) is a neuromodulator that mediates a great variety of functions both in the central and peripheral nervous system. It has also been shown that 5-HT can act as a growth and differentiation signal during embryogenesis.
In our laboratory it has been demonstrated that during the embryonic development of Xenopus laevis the 5-HT2B receptor gene is expressed in the retina, in the periocular mesenchyme and in the cranial neural crests. Functional experiments have shown that the 5-HT2B receptor is involved in the retinal and craniofacial morphogenesis.
In my thesis work I focused on the role of the 5-HT2B receptor in the periocular mesenchyme that represents a key signaling center required for a correct eye morphogenesis.
In the periocular mesenchyme the Pitx2 homeobox gene is also expressed. It encodes for a transcription factor that controls the development of the ocular anterior segment structures, such as the cornea, the choroid and the sclera. Pitx2 gene mutations in humans cause the Axenfeld-Rieger’s syndrome, an autosomal dominant disorder that results in microftalmia and developmental defects within the anterior segment of the eye and that may lead to blindness, caused by glaucoma, in 50% of the affected individuals.
On the basis of these data I have studied a possible correlation between the activity of the 5-HT2B receptor and the expression of the Pitx2 homeobox gene during eye development in the model organism Xenopus laevis. I have carried out 5-HT2B gene gain and loss of function experiments through micro-injections of an antisense oligonucleotide (morpholino) or of the corresponding in vitro transcribed mRNA. The resulting phenotypes have been analysed at molecular level through
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IV whole mount in situ hybridization with specific gene markers and through whole mount immunohistochemistry.
The obtained results show that the disregulation of the 5-HT2B gene expression causes defects in the neural crest cells of the periocular mesenchyme that express Pitx2 as well as defects in the closure of the optic fissure and in the spatial organization of the extrinsic ocular muscles.
These data suggest that the 5-HT2B receptor signaling can modulate the function of the neural crest component of the periocular mesenchyme contributing to a correct eye morphogenesis. Further studies will be necessary to get light on the molecular mechanisms underlying this function.
