Biology Department, Loyola University Chicago, Chicago, IL 60660, USA.
Dev Neurosci. 2010 Aug;32(3):184-96. doi: 10.1159/000313902. Epub 2010 Jul 20.
Geniculate axons are initially guided to discrete epithelial placodes in the lingual and palatal epithelium that subsequently differentiate into taste buds. In vivo approaches show that brain-derived neurotrophic factor (BDNF) mRNA is concentrated in these placodes, that BDNF is necessary for targeting taste afferents to these placodes, and that BDNF misexpression disrupts guidance. We used an in vitro approach to determine whether BDNF may act directly on geniculate axons as a trophic factor and as an attractant, and whether there is a critical period for responsiveness to BDNF. We show that BDNF promotes neurite outgrowth from geniculate ganglion explants dissected from embryonic day (E) 15, E18, infant, and adult rats cultured in collagen gels, and that there is a concentration optimum for neurite extension. Gradients of BDNF derived from slow-release beads caused the greatest bias in neurite outgrowth at E15, when axons approach the immature gustatory papillae. Further, neurites advanced faster toward the BDNF bead than away from it, even if the average amount of neurotrophic factor encountered was the same. We also found that neurites that contact BDNF beads did not advance beyond them. At E18, when axons would be penetrating pregustatory epithelium in vivo, BDNF continued to exert a tropic effect on geniculate neurites. However, at postnatal and adult stages, the influence of BDNF was predominantly trophic. Our data support a role for BDNF acting as an attractant for geniculate axons during a critical period that encompasses initial targeting but not at later stages.
膝状神经节轴突最初被引导到舌和腭上皮中的离散上皮基板，这些基板随后分化为味蕾。体内方法表明，脑源性神经营养因子（BDNF）mRNA 集中在这些基板中，BDNF 对于将味觉传入纤维靶向这些基板是必需的，BDNF 的错误表达会破坏导向。我们使用体外方法来确定 BDNF 是否可以作为营养因子和趋化因子直接作用于膝状神经节轴突，以及对 BDNF 反应是否存在关键时期。我们表明，BDNF 促进了从胚胎期（E）15、E18、婴儿和成年大鼠的膝状神经节神经节外植体在胶原凝胶中培养的神经突生长，并且存在神经突延伸的浓度最佳值。从缓释珠衍生的 BDNF 梯度导致 E15 时神经突生长的最大偏差，此时轴突接近未成熟的味觉乳头。此外，即使遇到的神经营养因子的平均数量相同，神经突也会更快地朝着 BDNF 珠前进，而不是远离它。我们还发现，接触 BDNF 珠的神经突不会超过它们前进。在 E18 时，当轴突在体内穿透预味觉上皮时，BDNF 继续对膝状神经节神经突发挥营养作用。然而，在出生后和成年阶段，BDNF 的影响主要是营养性的。我们的数据支持 BDNF 作为一个关键时期的趋化因子，在这个时期包括最初的靶向，但不包括后期的靶向，对膝状神经节轴突起作用。
