Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA Rocky Mountain Taste and Smell Center, University of Colorado School of Medicine, Aurora, CO 80045, USA Graduate Program in Cell Biology, Stem Cells and Development, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Program in Craniofacial and Mesenchymal Biology and Department of Orofacial Sciences, University of California San Francisco, San Francisco, CA 94131, USA.
Development. 2014 Aug;141(15):2993-3002. doi: 10.1242/dev.107631. Epub 2014 Jul 3.
Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.
味蕾是由伸长的上皮细胞组成的集合体，由味觉神经支配，味觉神经将味觉信息传递到脑干。味觉细胞通过上皮祖细胞的增殖在整个生命过程中不断更新，但这个过程的分子调控仍然未知。在胚胎发生过程中， sonic hedgehog (SHH) 负调控味蕾模式形成，因此抑制 SHH 会导致更多和更大的味蕾原基的形成，包括在舌头上通常没有味蕾的区域。在这里，我们使用 Cre-lox 系统来驱动 SHH 的组成型表达，以确定 SHH 对成年小鼠舌上皮的影响。我们表明，SHH 的异位表达改变了舌上皮细胞的命运，使得舌上皮祖细胞的子细胞形成细胞类型丰富的洋葱状味蕾，而不是非味觉的假复层上皮。这些 SHH 诱导的异位味蕾出现在以前认为不能产生味觉器官的成年舌区域。异位芽由所有味觉细胞类型组成，包括甜味、苦味、鲜味、咸味和酸味的支持细胞和检测器，并且重现了内源性味蕾的分子分化过程。然而，与内源性味蕾已确立的神经依赖性不同，异位芽的形成独立于味觉和躯体感觉神经支配。由于内源性味蕾的 SHH 表达需要神经支配，我们的数据表明，SHH 可以取代神经支配的需要，以驱动整个味蕾分化程序。
