Role of Serotonin Signaling in the Remodeling of Thioridazine‐Induced Craniofacial Deformities in Xenopus laevis Pre‐metamorphic Tadpoles

Craniofacial abnormalities have recently been given special attention because of a rise in the number of microcephaly cases associated with the spread of the Zika virus. Microcephaly, however, is just one of various common craniofacial deformities that can occur in vertebrates during development. Since craniofacial development is well‐conserved across vertebrates, numerous model organisms can be utilized to study craniofacial development. To that end, our lab takes advantage of the tractable amphibian model system, Xenopus laevis . Our recent studies revealed pre‐metamorphic Xenopus tadpoles can self‐correct craniofacial defects induced by exposure to thioridazine HCl, a D 2 dopamine receptor antagonist. The underlying molecular mechanism mediating this correction is unknown, and is thus the focus of our current work. Previously the Levin lab discovered that several developmental events, including the regulation of organ placement and cell movements during gastrulation, are mediated by neurotransmitters during development. Since the self‐correction of craniofacial defects includes both cell movement and tissue positioning, we are currently investigating whether the remodeling response is initiated and/or mediated by neurotransmitter‐dependent cellular pathways. Our current study utilized fluoxetine, a selective serotonin reuptake inhibitor, to block a candidate pathway throughout pre‐metamorphic stages in tadpoles. These experiments will help elucidate which signaling mechanism directs the correction of malformed craniofacial structures in tadpoles during pre‐metamorphic stages. Support or Funding Information The Paul G. Allen Frontiers Group, National Science Foundation, and American Society of Biochemistry and Molecular Biology