Department of Orofacial Sciences and Program in Craniofacial and Mesenchymal Biology, University of California San Francisco, San Francisco, California, USA.
PLoS Genet. 2011 Jun;7(6):e1002098. doi: 10.1371/journal.pgen.1002098. Epub 2011 Jun 2.
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.
味觉对于我们摄取营养物质和检测及避免潜在有毒物质的能力至关重要。感觉味蕾位于由上皮基板发育而来的乳突中。三种不同类型的味觉乳突位于啮齿动物舌头上:小菌状乳突位于舌前,而舌后含有较大的叶状乳突和一个单一的中线环状乳突(CVP)。尽管哺乳动物中 CVP 的数量存在很大差异,但它在味觉功能中的重要性以及作为最大的味觉乳突,人们对这种结构的发育知之甚少。在这里,我们报告说,Sprouty(Spry)基因和 Fgf10 之间的平衡,分别拮抗和激活受体酪氨酸激酶(RTK)信号,调节 CVP 的数量。单独缺失 Spry2 会导致 CVP 重复,这是由于基板祖细胞场的大小增加所致,而 Spry1(-/-);Spry2(-/-)胚胎有多个 CVP,表明 Sprouty 基因在调节祖细胞场大小方面具有冗余性。相比之下,缺失 Fgf10 会导致 CVP 缺失,这表明 FGF10 是味觉乳突的第一个诱导性、间质衍生的因子。我们的研究结果首次证明了上皮-间充质 FGF 信号在味觉乳突发育中的作用,表明 FGF 信号对祖细胞场大小的调节是乳突数量的关键决定因素,并表明哺乳动物物种中 CVP 数量的巨大差异可能与 FGF 途径的信号水平有关。