Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor
Neurotrophin-4 regulates the survival of gustatory neurons earlier in development using a different mechanism than brain-derived neurotrophic factor
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DOI：
10.1016/j.ydbio.2012.02.008
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发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Krimm, Robin F.
中科院分区：
文献类型：
--
作者：
Patel, Ami V.;Krimm, Robin F.
可用于神经支配味蕾的膝状体神经节中的神经元的数量由神经营养素-4（NT-4）和脑源性神经营养因子（BDNF）调节。我们目前的研究目标是研究发育过程中NT-4介导的膝状体神经元数量调节的时间和机制。我们发现NT-4突变小鼠在E10.5和E11.5之间失去了33%的膝状体神经元细胞。到E11.5，膝状体轴突刚刚到达舌头，还没有支配它们的味觉目标;因此，NT-4不起靶源性生长因子的作用。在E11.5时，在NT-4突变体和野生型神经节之间的增殖细胞或细胞退出细胞周期的速率中没有观察到差异。相反，TUNEL标记增加，表明与野生型相比，Ntf 4（-/-）小鼠的细胞死亡增加。然而，激活的caspase-3，这是上调的BDNF的情况下，没有增加。这一发现表明，由NT-4去除启动的细胞死亡通过与BDNF去除不同的细胞死亡途径发生。我们在Ntf 4（-/-）小鼠中没有观察到额外的味蕾或神经元的出生后损失。因此，在早期胚胎发育过程中，神经节和沿着投射途径产生的NT-4通过激活的半胱天冬酶-3非依赖性机制抑制细胞死亡。因此，与BDNF相比，NT-4在味觉发育中起着不同的作用;差异包括时间，神经营养因子的来源和作用机制。爱思唯尔公司出版
The number of neurons in the geniculate ganglion that are available to innervate taste buds is regulated by neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF). Our goal for the current study was to examine the timing and mechanism of NT-4-mediated regulation of geniculate neuron number during development. We discovered that NT-4 mutant mice lose 33% of their geniculate neuronal cells between E10.5 and E11.5. By E11.5, geniculate axons have just reached the tongue and do not yet innervate their gustatory targets; thus, NT-4 does not function as a target-derived growth factor. At E11.5, no difference was observed in proliferating cells or the rate at which cells exit the cell cycle between NT-4 mutant and wild type ganglia. Instead, there was an increase in TUNEL-labeling, indicating an increase in cell death in Ntf4(-/-) mice compared with wild types. However, activated caspase-3, which is up-regulated in the absence of BDNF, was not increased. This finding indicates that cell death initiated by NT-4-removal occurs through a different cell death pathway than BDNF-removal. We observed no additional postnatal loss of taste buds or neurons in Ntf4(-/-) mice. Thus, during early embryonic development, NT-4 produced in the ganglion and along the projection pathway inhibits cell death through an activated caspase-3 independent mechanism. Therefore, compared to BDNF, NT-4 plays distinct roles in gustatory development; differences include timing, source of neurotrophin, and mechanism of action. Published by Elsevier Inc.