Development of the Sense of Taste

描述（由申请人提供）：为了发展对味觉至关重要的神经回路，味觉神经元和相关的体感神经节必须将神经突延伸到舌头，并与味觉乳头器官及其常驻味蕾建立联系。在这个提议中，实验室继续对味觉发育的研究，重点关注支配味觉乳头的两个神经节，神经节和三叉神经节，以及这些神经节的靶器官，真菌状乳头本身。目的是测试关于神经营养分子家族如何改变神经节神经生理的假设；辨别调节乳头发育的分子；确定调控分子和靶组织对神经支配神经节功能分化的影响。使用体外方法，包括胚胎神经节外植体的隔室培养系统，以允许神经元细胞体或体细胞与从体细胞生长的神经突分开的分子维持，并随后进行电生理记录；以及整个胚胎鼠舌的器官培养。这些体外系统使研究分子对发育中的味觉系统细胞功能的影响成为可能。目的1验证神经营养因子在神经节和乳头靶器官中具有独特的空间和时间模式的假设，以及在神经节体和生长的神经突中单独和特异性的神经营养因子暴露会影响神经节神经元的电生理特性。目的2测试了一种假设，即称为形态因子的特殊信号分子如何调节真菌状乳头的形成和舌头上乳头的模式分布。目的3通过验证舌分子调节乳头发育也可以影响支配乳头的神经节神经元的神经生理特性的假设，统一了其他两个特定目的。在Aim 3中，另一个假设是在隔室培养中测试靶组织和非靶组织对神经节神经元电生理的影响。研究神经节神经生理学的隔室培养方法是味觉领域的新方法，它提供了用最佳存活分子维持神经元细胞体的机会，同时用胚胎舌头中存在的分子和组织挑战正在生长的神经突。Aim 2中使用的全舌培养提供了直接实验操作和评估图案乳头阵列的能力，这在其他模型中是不可用的。很少有实验室关注于味觉系统中发育中的神经元和感觉器官的研究。然而，这些研究对于充分理解味觉是必不可少的，因为味觉刺激着我们的食物选择，从而调节着健康或不健康的饮食模式。

DESCRIPTION (provided by applicant): To develop neural circuits that are essential for taste sensation, neurons in taste and associated somatosensory sensory ganglia must extend neurites to the tongue and make connections with the taste papilla organs and their resident taste buds. In this proposal, the laboratory continues studies of taste development to focus on two ganglia that innervate taste papillae, the geniculate and trigeminal ganglia, and the target organs of these ganglia, the fungiform papillae per se. Goals are to test hypotheses about how the family of neurotrophin molecules modifies ganglion neurophysiology; to discern molecules that regulate papilla development; and, to determine effects of regulatory molecules and target tissues on functional differentiation of innervating ganglia. In vitro approaches are used, including a compartment culture system for embryonic ganglion explants to permit separate molecular maintenance of the neuron cell body, or soma, versus the neurites that grow from the soma, and subsequent electrophysiological recording; and, organ cultures of the entire embryonic rat tongue. These in vitro systems make possible study of molecular affects on cell function in the developing taste system. Aim 1 test hypotheses that neurotrophins have distinctive spatial and temporal patterns in ganglia and papilla target organs, and that separate and specific neurotrophin exposure at ganglion soma versus growing neurites affects the electrophysiological properties of the ganglion neurons. Aim 2 tests hypotheses about how special signaling molecules called morphogens can regulate formation of fungiform papillae and the patterned distribution of papillae on the tongue. Aim 3 unifies the other two specific aims by testing hypotheses that lingual molecules regulating papilla development can also affect neurophysiological properties of the ganglion neurons that innervate papillae. In Aim 3, an additional hypothesis is to test effects of target and non-target tissues on electrophysiology of ganglion neurons, in compartment cultures. The compartment culture approach to study of ganglion neurophysiology is new to the taste field, and affords opportunities to maintain the neuron cell body with optimal survival molecules, while challenging the growing neurites with molecules and tissues that are present in the embryonic tongue. The whole tongue culture used in Aim 2 provides capability for direct experimental manipulation and evaluation of patterned papilla arrays, not available with other models. There are very few laboratories focused on study of developing neurons and sensory organs in the taste system. Yet such studies are essential for a full understanding of the sense of taste, which motivates our food choices and thereby mediates healthy or unhealthy diet patterns.