Serotonin 2B receptor signaling is required for craniofacial morphogenesis and jaw joint formation in Xenopus.
Serotonin (5-HT) is a neuromodulator that plays many different roles in adult and embryonic life. Among the 5-HT receptors, 5-HT2B is one of the key mediators of 5-HT functions during development. We used Xenopus laevis as a model system to further investigate the role of 5-HT2B in embryogenesis, focusing on craniofacial development. By means of gene gain- and loss-of-function approaches and tissue transplantation assays, we demonstrated that 5-HT2B modulates, in a cell-autonomous manner, postmigratory skeletogenic cranial neural crest cell (NCC) behavior without altering early steps of cranial NCC development and migration. 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 and for shaping the mandibular arch skeletal elements. In particular, 5-HT2B signaling is required to define and sustain the Xbap expression necessary for jaw joint formation. To shed light on the molecular identity of the transduction pathway acting downstream of 5-HT2B, we analyzed the function of phospholipase C beta 3 (PLC) in Xenopus development and showed that PLC is the effector of 5-HT2B during craniofacial development. Our results unveiled an unsuspected role of 5-HT2B in craniofacial development and contribute to our understanding of the interactive network of patterning signals that is involved in the development and evolution of the vertebrate mandibular arch.
Reisoli
Elisa
E
Unità di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Università di Pisa, S.S.12 Abetone e Brennero 4, Pisa, Italy.
De Lucchini
Stefania
S
Nardi
Irma
I
Ori
Michela
M
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D005147:Facial Bones / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D007596:Joints / Q000196:embryology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044403:Receptor, Serotonin, 5-HT2B / Q000235:genetics / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists; D015398:Signal Transduction; D012886:Skull / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D054799:Phospholipase C beta; D012333:RNA, Messenger; D044403:Receptor, Serotonin, 5-HT2B; D058830:Serotonin 5-HT2 Receptor Antagonists; D014157:Transcription Factors; D029867:Xenopus Proteins; C498768:Hand2 protein, Xenopus; C104164:NKX3-2 protein, Xenopus