Interactions between RA and FGF signaling in vertebrate patterning

Blumberg博士感兴趣的是确定维甲酸(RA)和成纤维细胞生长因子8(FGF8)在胎盘前神经外胚层(PPE)形成过程中如何相互拮抗S的活性。PPE产生了感觉安慰剂，它后来成为头部的感官器官，包括眼睛、耳朵和嗅觉系统。PPE的边界是如何建立的尚不清楚，但这些边界调节着感觉安慰剂的大小。因此，确定相反的RA和FGF8信号如何调节PPE的建立，将为感觉器官如何发育提供关键信息。Blumberg博士提出，两个基因，TBX1和Frontline，介导了RA对FGF8信号的影响。将使用生物化学和分子方法来测试这些基因在利用两栖动物非洲爪哇建立PPE过程中的功能。非洲爪哇胚胎在发育的最早阶段就可以获得，在活的胚胎中，感兴趣的基因的表达可以迅速增加或减少，以测试它们的功能。预期的结果是确定了建立PPE边界的分子通路，这将适用于理解其他过程中相反的RA-FGF8信号。理论上的价值在于，这些研究将揭示RA和FGF8是如何相互调节S的活动的，从而更好地理解胚胎细胞是如何决定是分裂还是分化为成年细胞类型。更广泛的影响是在教育、指导和一般社会福利领域。PI致力于本科生和研究生教育，并有培训代表不足的少数民族学生的记录。这个项目通过加深我们对RA和FGF8如何调节基本生物过程的理解而造福于社会。

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.