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在缺乏TrkB配体脑源性神经营养因子(BDNF)和神经营养因子-4(NT-4)的情况下味觉乳头和味蕾的发育与维持

Gustatory papillae and taste bud development and maintenance in the absence of TrkB ligands BDNF and NT-4.

作者信息

Ito Akira, Nosrat Christopher A

机构信息

Department of Restorative Dentistry, College of Dentistry, and Center for Cancer Research, University of Tennessee Health Science Center, Cancer Research Building, Room 120, Memphis, TN 38163, USA.

出版信息

Cell Tissue Res. 2009 Sep;337(3):349-59. doi: 10.1007/s00441-009-0833-7. Epub 2009 Jul 23.

Abstract

Taste buds and the peripheral nerves innervating them are two important components of the peripheral gustatory system. They require appropriate connections for the taste system to function. Neurotrophic factors play crucial roles in the innervation of peripheral sensory organs and tissues. Both brain-derived neurotrophic factor (BDNF) null-mutated and neurotrophin-4 (NT-4) null-mutated mice exhibit peripheral gustatory deficits. BDNF and NT-4 bind to a common high affinity tyrosine kinase receptor, TrkB (NTRK-2), and a common p75 neurotrophin receptor (NGFR). We are currently using a transgenic mouse model to study peripheral taste system development and innervation in the absence of both TrkB ligands. We show that taste cell progenitors express taste cell markers during early stages of taste bud development in both BDNF(-/-)xNT-4(-/-) and wild-type mice. At early embryonic stages, taste bud progenitors express Troma-1, Shh, and Sox2 in all mice. At later stages, lack of innervation becomes a prominent feature in BDNF(-/-)xNT-4(-/-) mice leading to a decreasing number of fungiform papillae and morphologically degenerating taste cells. A total loss of vallate taste cells also occurs in postnatal transgenic mice. Our data indicate an initial independence but a later permissive and essential role for innervation in taste bud development and maintenance.

摘要

味蕾及其支配神经是外周味觉系统的两个重要组成部分。味觉系统要发挥功能,它们需要适当的连接。神经营养因子在外周感觉器官和组织的神经支配中起关键作用。脑源性神经营养因子(BDNF)基因敲除小鼠和神经营养因子-4(NT-4)基因敲除小鼠均表现出外周味觉缺陷。BDNF和NT-4与共同的高亲和力酪氨酸激酶受体TrkB(NTRK-2)和共同的p75神经营养因子受体(NGFR)结合。我们目前正在使用转基因小鼠模型研究在缺乏两种TrkB配体的情况下外周味觉系统的发育和神经支配。我们发现,在BDNF(-/-)xNT-4(-/-)小鼠和野生型小鼠的味蕾发育早期阶段,味觉细胞祖细胞均表达味觉细胞标志物。在胚胎早期阶段,所有小鼠的味蕾祖细胞均表达Troma-1、Shh和Sox2。在后期阶段,缺乏神经支配成为BDNF(-/-)xNT-4(-/-)小鼠的一个突出特征,导致菌状乳头数量减少,味觉细胞形态退化。出生后的转基因小鼠还出现轮廓乳头味觉细胞完全缺失的情况。我们的数据表明,在味蕾发育和维持过程中,神经支配最初具有独立性,但后期具有许可性且必不可少。

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