5-HT2B-mediated serotonin signaling is required for eye morphogenesis in Xenopus

• Published in: Molecular and cellular neuroscience 2005-06, Vol.29 (2), p.299-312
• Main Authors: De Lucchini, Stefania, Ori, Michela, Cremisi, Federico, Nardini, Martina, Nardi, Irma
• Format: Article
• Language: English
• Subjects: Animals; Cell Proliferation; Cell Survival - physiology; Eye - cytology; Eye - embryology; Eye - growth & development; Eye Abnormalities - genetics; Eye Abnormalities - metabolism; Gene Expression Regulation, Developmental - physiology; Nerve Growth Factors - metabolism; Neural Pathways - abnormalities; Neural Pathways - cytology; Neural Pathways - metabolism; Organogenesis - physiology; Receptor, Serotonin, 5-HT2B - genetics; Receptor, Serotonin, 5-HT2B - metabolism; Retina - abnormalities; Retina - cytology; Retina - metabolism; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Messenger - pharmacology; Serotonin - metabolism; Signal Transduction - physiology; Stem Cells - cytology; Stem Cells - metabolism; Up-Regulation - physiology; Xenopus; Xenopus laevis - embryology; Xenopus laevis - growth & development; Xenopus laevis - metabolism
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2005.03.008

In this paper, we show that serotonin, via 5-HT2B receptor, is involved in Xenopus retinal histogenesis and eye morphogenesis by supporting cell proliferation and survival. To analyze the 5-HT2B function in retinal development, we performed a loss-of-function study using both a pharmacological and a morpholino antisense oligonucleotide approach. Gain-of-function experiments were made by microinjecting 5-HT2B mRNA. Misregulation of the 5-HT2B receptor activity causes alterations in the proliferation rate and survival of retinal precursors, resulting in abnormal retinal morphology, where lamination is severely compromised. Clones derived from lipofected retinoblasts that overexpress 5-HT2B show an increase in the relative percentage of ganglion cells, possibly due to protection from apoptosis. This effect is reversed in clones lipofected with a 5-HT2B-specific morpholino. We hypothesize that the survival of the correct number of ganglion cells is controlled by 5-HT/5-HT2B signaling. Serotonin, acting as a neurotrophic factor, may contribute by refining retinal connectivity and cytoarchitecture.