SEROTONIN 2B RECEPTOR SIGNALING IS REQUIRED FOR EYE MORPHOGENESIS IN XENOPUS

Serotonin (5-HT) is a neuromodulator that plays many roles in adult and embryonic life. Among the 5-HT receptors, 5-HT2B is one of the key mediators of 5-HT functions during develop- ment. We demonstrated that 5-HT2B modulates postmigratory skeletogenic cranial neural crest cell (NCC) behavior. 5-HT2B overexpression induced the formation of an ectopic visceral skeletal element and altered the dorsoventral patterning of the branchial arches. Loss-of-function experiments revealed that 5- HT2B signaling is necessary for jaw joint formation 1,2 . Moreover, 5-HT2B morphants have defective eyes with a loss of the ventral optic fissure closure (coloboma). Interestingly, the 5- HT2B gene is expressed both in the retina and in periocular mesenchyme (POM), a key signaling center required for eye morphogenesis. POM is composed by cranial NCC and cranial paraxial mesoderm derived cells. In 5-HT2B morphants the expression of key genes involved in POM development, such as Pitx2, FoxC1 and Raldh3, is affected. NCC remain gathered in the ventral part of the eye failing to conclude their migration within the optic fissure. POM also participates to the morpho- genesis of the optic nerve and periocular muscles that result affected in 5-HT2B morphants. Embryos pharmacological treatments, with a selective 5-HT2B antagonist, reproduce all the morphants phenotypes. By using NCCs transplantation assay and time laps in vivo analysis, we propose a dual role of 5-HT2B signaling in the retina and in the POM possibly cooperating to modulate different events of eye morphogenesis and optic fis- sure closure. These results unveil a new role for 5-HT2B signal- ing during development and propose it as a new possible target for congenital eye disease such as coloboma