Let\u27s face it : ǂb the teratogenic effects of polycyclic aromatic hydrocarbons on craniofacial development

The development of the craniofacial structures can be disrupted by exposure to teratogens such as polycyclic aromatic hydrocarbons (PAH’s) during embryogenesis. These defects can range from orofacial clefts to various other malformations of the head and jaw. PAHs such as Naphthalene (naph), are hazardous compounds which emerge due to the incomplete combustion of coal, tobacco, and other organic material (Langois et al., 2012). To evaluate the impact of environmental teratogens such as PAHs on embryonic development, we have taken advantage of the extrauterine development of the utilized zebrafish model system. We aim to identify the cellular and molecular processes that mediate PAH teratogenesis of the craniofacial system. The pharyngeal system is composed of three precursor structures and we postulate that naph can be acting upon these three cell types: the cranial NCCs which encompass the pharyngeal arches, the endodermal cells of the developing pharyngeal pouches, or epibranchial placodal cells that are known to interact with pouch and arch growth. Using various assays such as antibody and transgenic reporters for both arches and pouches, we demonstrate that naph causes specific malformations in the posterior most region of the pharyngeal system. Our data supports a model in which PAH mediated teratogenesis first targets the posterior pharyngeal arches that then indirectly impacts the formation of the pharyngeal pouches. Placodal cells do not appear to be involved. This model is supported by changes in the early expression of the arch marker dlx2a. It is our prediction that naph operates through the Aryl hydrocarbon receptor pathway to influence the molecular regulation of posterior arch formation. In order to confirm the exact point in which naph mediated teratogenesis occurs, we utilize live confocal imaging to 9 observe the dynamics of these cell types and how they are disrupted during exposure to naph. These results further suggestion that the observed morphological defects of craniofacial structures in zebrafish are due primarily to neural crest cell disruption