Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue
Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue
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DOI：
10.1006/dbio.2001.0190
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发表时间：
2001-04-15
影响因子：
2.7
通讯作者：
Albers, KM
中科院分区：
文献类型：
--
作者：
Krimm, RF;Miller, KK;Albers, KM
脑源性神经营养因子 (BDNF) 和神经营养蛋白-IL (NT4) 对于膝状神经节神经元的生存至关重要，膝状神经节神经元为前舌和上腭的味蕾提供感觉传入。为了确定这些靶标衍生的生长因子如何调节味觉发育，在舌头基底上皮细胞中过度表达 BDNF (BDNF-OE) 或 NT4 (NT4-OE) 的转基因小鼠中检查了味觉系统。 BDNF 或 NT4 的过度表达导致膝状神经节神经元数量分别增加 93% 和 140%。令人惊讶的是，两种转基因品系的菌状乳头和味蕾数量都严重减少，主要是在舌背中部区域和腹侧尖端。周围乳头或切端乳头的味蕾没有观察到改变。菌状乳头最初出现在新生 BDNF-OE 动物的舌头上，但许多很小，神经支配较差，并在出生后消失。为了解释菌状乳头神经支配的丧失，用亲脂性示踪剂 DiI 标记发育中动物的面神经。与味觉神经元仅支配菌状乳头的对照小鼠相比，BDNF-OE和NT4-OE小鼠的味觉神经元支配很少的菌状乳头。相反，一些纤维接近但没有穿透上皮，并且观察到丝状乳头的异常神经支配。此外，转基因小鼠中形成的一些乳头有两个味蕾（而不是一个），并且经常排列成两个或三个乳头簇。这些结果表明，靶源性 BDNF 和 NT4 不仅是膝状神经节神经元的生存因子，而且在调节菌状乳头的发育和空间模式以及将味觉神经元靶向这些感觉结构方面具有重要作用。 (C) 2001 年学术出版社。
Brain-derived neurotrophic factor (BDNF) and neurotrophin-il (NT4) are essential for the survival of geniculate ganglion neurons, which provide the sensory afferents for taste buds of the anterior tongue and palate. To determine how these target-derived growth factors regulate gustatory development, the taste system was examined in transgenic mice that overexpress BDNF (BDNF-OE) or NT4 (NT4-OE) in basal epithelial cells of the tongue. Overexpression of BDNF or NT4 caused a 93 and 140% increase, respectively, in the number of geniculate ganglion neurons. Surprisingly, both transgenic lines had severe reduction in fungiform papillae and taste bud number, primarily in the dorsal midregion and ventral tip of the tongue. No alterations were observed in taste buds of circumvallate or incisal papillae. Fungiform papillae were initially present on tongues of newborn BDNF-OE animals, but many were small, poorly innervated, and lost postnatally. To explain the loss of nerve innervation to fungiform papillae, the facial nerve of developing animals was labeled with the lipophilic tracer DiI. In contrast to control mice, in which taste neurons innervated only fungiform papillae, taste neurons in BDNF-OE and NT4-OE mice innervated few fungiform papillae. Instead, some fibers approached but did not penetrate the epithelium and aberrant innervation to filiform papillae was observed. In addition, some papillae that formed in transgenic mice had two taste buds (instead of one) and were frequently arranged in clusters of two or three papillae. These results indicate that target-derived BDNF and NT4 are not only survival factors for geniculate ganglion neurons, but also have important roles in regulating the development and spatial patterning of fungiform papilla and targeting of taste neurons to these sensory structures. (C) 2001 Academic Press.