A 28-year-old man with a history of mycosis fungoides presented for evaluation of multiple dark-brown macules and hyperpigmented dome-shaped papules on the distal tongue. A shave biopsy of the tongue revealed melanin pigment in the basal keratinocytes and melanophages in the lamina propria, consistent with pigmented fungiform papillae of the tongue. Relevant clinical and histologic features of this diagnosis are reviewed.

The sense of taste is fundamental to our ability to ingest nutritious substances and to detect and avoid potentially toxic ones. Sensory taste buds are housed in papillae that develop from epithelial placodes. Three distinct types of gustatory papillae reside on the rodent tongue: small fungiform papillae are found in the anterior tongue, whereas the posterior tongue contains the larger foliate papillae and a single midline circumvallate papilla (CVP). Despite the great variation in the number of CVPs in mammals, its importance in taste function, and its status as the largest of the taste papillae, very little is known about the development of this structure. Here, we report that a balance between Sprouty (Spry) genes and Fgf10, which respectively antagonize and activate receptor tyrosine kinase (RTK) signaling, regulates the number of CVPs. Deletion of Spry2 alone resulted in duplication of the CVP as a result of an increase in the size of the placode progenitor field, and Spry1(-/-);Spry2(-/-) embryos had multiple CVPs, demonstrating the redundancy of Sprouty genes in regulating the progenitor field size. By contrast, deletion of Fgf10 led to absence of the CVP, identifying FGF10 as the first inductive, mesenchyme-derived factor for taste papillae. Our results provide the first demonstration of the role of epithelial-mesenchymal FGF signaling in taste papilla development, indicate that regulation of the progenitor field size by FGF signaling is a critical determinant of papilla number, and suggest that the great variation in CVP number among mammalian species may be linked to levels of signaling by the FGF pathway.

Oral disease continues to be an epidemic in the U.S., affecting people of all age groups. Dental Caries is the single most common chronic childhood disease--five times more chronic than asthma. Oral and pharyngeal cancers are diagnosed in about 30,000 Americans annually, mostly in the elderly and with poor prognosis. Studies have shown a link between periodontal diseases and a variety of other medical problems such as diabetes, cardiovascular disease, stroke, and adverse pregnancy outcomes. In addition, oral disease can greatly affect our quality of life given that it can affect our ability to eat, the types of foods we choose to eat, our facial appearance, and our ability to communicate. In the last decade, there has been recognition on the neglect of oral health in medical training and in medicine due to the separation of oral health from systemic health. Some additional barriers to oral health include a lack of access to care (due to limited income or lack of insurance), transportation, or the flexibility to take time off from work or leave other responsibilities. According to the CDC, iti s found that people of color (particularly black and Hispanic), poverty, low income, modest education, and disability have higher oral disease rates than more socially advantaged populations. Often times these patients rely on their primary care provider for their oral health. That is why many initiatives have been developed to provide educational resources to enhance the role of the clinician's training in the promotion of oral health. With these initiatives including the development of this study guide, there is hope that we will begin to see better outcomes in our patients through better trained medical providers.

Many vertebrate organ systems contain a specialized ciliated epithelium decorated with motile cilia, which produce a ciliary flow in order to move mucus or fluid across the tissue surface. Examples include the proximal airways of the respiratory tract, oviduct, ependyma of the brain ventricles and the embryonic node. The importance motile cilia function in these specialized tissues to organ function is evident from human diseases such as primary ciliary dyskinesia (PCD) or immotile cilia syndrome. Patients with PCD are prone to chronic respiratory infections, sinus infections, in 50% of cases have situs inversus and in rare cases exhibit hydrocephalus. This broad array of phenotypes due to ciliary dysfunction clearly shows the importance of ciliated epithelia to organismal survival. A great deal is known about ciliary flow and how it relates to tissue function in relation to disease states. However, much less is known about how such tissues are formed during development, and what factors control the formation of cilia in these tissues. In this work I first describe the morphogenesis of the ciliated external epithelium of Xenopus laevis embryos, a tissue that closely resembles the respiratory epithelium in form and function. Cells with motile cilia cover the Xenopus embryo in a characteristic spacing pattern. This pattern arises early in development when cells in the inner layer of the ectoderm are selected by Notch signaling to form ciliated cell precursors (CCPs) that then undergo radial intercalation into the outer epithelial layer to form ciliated cells. Inhibition of Notch signaling results in an overproduction of CCPs; while radial intercalation becomes limiting ciliated cells maintain their spacing in the epithelium. Transgenic and transplantation assays to mark ciliated cells and intercalating populations, respectively, indicate that intercalating cells are free to wedge basolaterally, but can only insert apically at vertices where multiple outer cells make contact, likely making apical insertion the rate-limiting step during radial intercalation. Ciliated cell spacing also appears to be influenced by several other factors including competition with intercalating non-ciliated cell populations for vertices, cell morphology, and limitations on apical insertion likely imposed by the outer layer. Suggesting that cells other than the ciliated cells themselves can affect the ciliated cell spacing pattern, and thus final tissue architecture observed in such an epithelium. In the second part of this dissertation I describe a role for FoxJ1, a forkhead transcription factor, in the specification of node-like cilia in Xenopus and zebrafish embryos. Monociliate cells at the embryonic node generate a leftward fluid flow responsible for left-right asymmetry breaking in mouse, fish and Xenopus embryos. These cilia share features of both primary sensory cilia and motile cilia found on multiciliate cells, but how these cilia are specified in relation to other cilia is unknown. Using knockdown by morpholino injection, I show that FoxJ1 plays a conserved role in basal body docking in multiciliate cells found on the external epithelium of Xenopus embryos. However, in contrast to results in the mouse, I also show that FoxJ1 is required for formation of the node-like cilia in Xenopus gastrocoel roof plate (GRP) and zebrafish Kupffer's vesicle. Additionally, I show that misexpression of FoxJ1 is sufficient to induce ectopic GRP -like cilia on the surface epithelial cells of Xenopus embryos. Microarray analysis further indicates that FoxJ1 can induce ectopic cilia formation by upregulating the expression of genes required for cilia structure as well as genes required for cilia motility. Together these results indicate that node-like cilia in Xenopus and zebrafish are likely generated using a genetic pathway similar to that used to specify cilia in multiciliate cells. The studies presented in this dissertation shed light on the both the morphogenetic events that underlies the formation of the ciliated external epithelium in Xenopus embryos, but also on the specification of two different cilia subtypes that form on the epithelia of developing Xenopus embryo