Recent work from our laboratory focused on the role of the serotonin 5-HT2B receptor in Xenopus craniofacial and ocular morphogenesis. 5-HT2B gene is, in fact, expressed in the cranial neural crest cells (NCCs) which contribute to visceral arches and periocular mesenchyme (POM), a key signaling center required for eye morphogenesis including the choroid fissure closure. We demonstrated that pharmacologic and genetic alterations in 5-HT2B signaling cause ocular dysgenesis, characterized by small and dorsalized eyes, disorganized extraocular muscles, a shorter optic nerve and a failure of the choroid fissure closure or coloboma. To gain insight into the molecular mechanisms of 5 -HT2B signaling in eye morphogenesis, we analyzed the gene expression profile of a number of key genes involved in POM development by in situ hybridization and qPCR in 5-HT2B morphants. POM specific genes such as Pitx2 and Foxc2, known to be regulated by the retinoic acid (RA), were upregulated and showed altered expression patterns. Twist, a marker of NCCs derived POM cells, revealed an accumulation of NCCs around the eye and near the ocular fissure suggesting a possible alteration in NCCs migration during the optic fissure closure and anterior eye segment formation. The Vax2 gene, a marker of ventral retina did not change its expression domain. Interestingly, the expression of Raldh3, a RA generating enzyme, was upregulated in 5-HT2B morphants resulting in an expanded expression domain in the ventral retina. On the whole these data support the notion that 5-HT2B signaling has a key role in the molecular networks of extrinsic factors governing ocular morphogenesis and suggest a possible interaction between 5-HT and RA signaling during POM development.
Serotonin 2B receptor signaling is required for ocular morphogenesis in Xenopus.
DE LUCCHINI, STEFANIA;
2013
Abstract
Recent work from our laboratory focused on the role of the serotonin 5-HT2B receptor in Xenopus craniofacial and ocular morphogenesis. 5-HT2B gene is, in fact, expressed in the cranial neural crest cells (NCCs) which contribute to visceral arches and periocular mesenchyme (POM), a key signaling center required for eye morphogenesis including the choroid fissure closure. We demonstrated that pharmacologic and genetic alterations in 5-HT2B signaling cause ocular dysgenesis, characterized by small and dorsalized eyes, disorganized extraocular muscles, a shorter optic nerve and a failure of the choroid fissure closure or coloboma. To gain insight into the molecular mechanisms of 5 -HT2B signaling in eye morphogenesis, we analyzed the gene expression profile of a number of key genes involved in POM development by in situ hybridization and qPCR in 5-HT2B morphants. POM specific genes such as Pitx2 and Foxc2, known to be regulated by the retinoic acid (RA), were upregulated and showed altered expression patterns. Twist, a marker of NCCs derived POM cells, revealed an accumulation of NCCs around the eye and near the ocular fissure suggesting a possible alteration in NCCs migration during the optic fissure closure and anterior eye segment formation. The Vax2 gene, a marker of ventral retina did not change its expression domain. Interestingly, the expression of Raldh3, a RA generating enzyme, was upregulated in 5-HT2B morphants resulting in an expanded expression domain in the ventral retina. On the whole these data support the notion that 5-HT2B signaling has a key role in the molecular networks of extrinsic factors governing ocular morphogenesis and suggest a possible interaction between 5-HT and RA signaling during POM development.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
