Development of the Sense of Taste

描述(申请人提供)：为了发展味觉所必需的神经回路，味觉神经元和相关的体感感觉神经节必须将神经突起延伸到舌头，并与味觉乳头器官及其驻留的味蕾建立联系。在这个方案中，实验室继续研究味觉发育，重点放在两个支配味觉乳头的神经节，膝状神经节和三叉神经节，以及这些神经节的目标器官，菌状乳突本身。目的是测试有关神经营养因子家族如何改变神经节神经生理学的假说；识别调节乳头发育的分子；以及确定调节分子和靶组织对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胞体与从胞体长出的神经突起进行单独的分子维护，以及随后的电生理记录；以及整个胚胎大鼠舌部的器官培养。这些体外系统使得在味觉发育系统中研究分子对细胞功能的影响成为可能。目的1实验假设神经营养因子在神经节和乳头靶器官中具有不同的时空模式，神经节胞体和生长轴突的分离和特异性神经营养因子暴露影响神经节神经元的电生理特性。目的2检验被称为形态发生因子的特殊信号分子如何调节菌状乳头的形成和舌部乳头的图案化分布的假说。目的3通过测试语言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说，统一了另外两个特定的目的。在目标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。隔室培养方法用于神经节神经生理学的研究对味觉领域来说是新的，它提供了用最佳生存分子维持神经元细胞体的机会，同时用胚胎舌中存在的分子和组织来挑战正在生长的神经突起。AIM 2中使用的全舌培养提供了直接实验操作和评估图案化乳头阵列的能力，这是其他型号所不具备的。很少有实验室专注于味觉系统中发育的神经元和感觉器官的研究。然而，这样的研究对于充分理解味觉是必不可少的，味觉是我们选择食物的动力，从而调节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.