Interactions between RA and FGF signaling in vertebrate patterning

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Dr. Blumberg is interested in determining how retinoic acid (RA) and fibroblast growth factor 8 (FGF8) antagonize each other''s activity during formation of the pre-placodal neural ectoderm (PPE). The PPE gives rise to the sensory placodes, which later become the sensory organs of the head, including the eyes, ears, and olfactory system. How the boundaries of the PPE are established remains unclear, yet these boundaries regulate the size of the sensory placodes. Thus, determining how opposing RA and FGF8 signals regulate the establishment of the PPE will provide key information on how sensory organs develop. Dr. Blumberg proposes that two genes, Tbx1 and frontline, mediate the effects of RA on FGF8 signaling. Biochemical and molecular approaches will be used to test the function of these genes in establishing the PPE using the amphibian, Xenopus laevis. Xenopus embryos are accessible at the earliest stages of development and the expression of interesting genes can be rapidly increased or decreased in the living embryo to test their function. The expected results are the identification of the molecular pathways that establish the PPE boundaries which will be applicable to understanding opposing RA-FGF8 signals in other processes. The intellectual merit is that these studies will reveal how RA and FGF8 regulate each other''s activity, leading to a better understanding of how embryonic cells decide whether to divide or to differentiate into an adult cell type. The broader impacts are in the areas of education, mentoring, and general societal benefit. The PI is committed to undergraduate and graduate education and has a record of training under-represented minority students. This project benefits society by deepening our understanding of how RA and FGF8 regulate fundamental biological processes.