Prochazkova Michaela, Häkkinen Teemu J, Prochazka Jan, Spoutil Frantisek, Jheon Andrew H, Ahn Youngwook, Krumlauf Robb, Jernvall Jukka, Klein Ophir D
Department of Orofacial Sciences and Program in Craniofacial Biology, University of California San Francisco, San Francisco, CA 94143, USA.
Institute of Molecular Genetics of the CAS, v. v. i., Czech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Division BIOCEV, Prumyslova 595, Vestec 252 42, Czech Republic.
Development. 2017 Jun 15;144(12):2212-2221. doi: 10.1242/dev.148080. Epub 2017 May 15.
The patterning of repeated structures is a major theme in developmental biology, and the inter-relationship between spacing and size of such structures is an unresolved issue. Fungiform papillae are repeated epithelial structures that house taste buds on the anterior tongue. Here, we report that FGF signaling is a crucial regulator of fungiform papillae development. We found that mesenchymal FGF10 controls the size of the papillary area, while overall patterning remains unchanged. Our results show that FGF signaling negatively affects the extent of canonical Wnt signaling, which is the main activation pathway during fungiform papillae development; however, this effect does not occur at the level of gene transcription. Rather, our experimental data, together with computational modeling, indicate that FGF10 modulates the range of Wnt effects, likely via induction of expression. We suggest that modification of the reach of Wnt signaling could be due to local changes in morphogen diffusion, representing a novel mechanism in this tissue context, and we propose that this phenomenon might be involved in a broader array of mammalian developmental processes.
重复结构的模式形成是发育生物学中的一个主要主题,而这些结构的间距和大小之间的相互关系是一个尚未解决的问题。菌状乳头是重复的上皮结构,位于舌前部,其中含有味蕾。在此,我们报告成纤维细胞生长因子(FGF)信号是菌状乳头发育的关键调节因子。我们发现间充质FGF10控制乳头区域的大小,而整体模式保持不变。我们的结果表明,FGF信号对经典Wnt信号的程度产生负面影响,而Wnt信号是菌状乳头发育过程中的主要激活途径;然而,这种影响并非发生在基因转录水平。相反,我们的实验数据与计算模型表明,FGF10可能通过诱导表达来调节Wnt效应的范围。我们认为Wnt信号作用范围的改变可能是由于形态发生素扩散的局部变化,这代表了这种组织环境中的一种新机制,并且我们提出这种现象可能涉及更广泛的哺乳动物发育过程。