The zinc finger transcription factor Klf7 is required for TrkA gene expression and development of nociceptive sensory neurons
The zinc finger transcription factor Klf7 is required for TrkA gene expression and development of nociceptive sensory neurons
复制标题
DOI：
10.1101/gad.1227705
复制
发表时间：
2005-06-01
影响因子：
10.5
通讯作者：
Parada, LF
中科院分区：
文献类型：
--
作者：
Lei, L;Laub, F;Parada, LF
TrkA 是神经生长因子 (NGF) 的高亲和力受体，对于伤害性感觉神经元和交感神经元的发育至关重要。锌指转录因子 Klf7 与 TrkA 最小增强子的重要顺式元件相互作用，并在这些神经元中与 TrkA 共表达。我们发现 KIf7 与内源性 TrkA 最小增强子结合，并且可以以序列依赖性方式激活 TrkA 最小增强子的转录。在 KIf7(-/-) 新生小鼠中，我们发现由于细胞凋亡增加，感觉神经元显着减少。神经元损失仅限于通常依赖 TrkA 提供神经营养支持的伤害性神经元，而其他体感神经元群则表现正常。感觉神经元中 TrkA 表达的减少是 KIf7 基因消融的直接作用，而不是细胞死亡的继发作用。结果，KIf7(-/-)小鼠对有害刺激的反应不足。最后，去除一个TrkA等位基因会加剧KIf7(-/-)小鼠中TrkA(+)神经元的丧失。因此，KIf7 特异性调节 TrkA 基因表达，并且是伤害性感觉神经元子集发育所必需的。
TrkA, the high affinity receptor for nerve growth factor (NGF), is essential for the development of nociceptive sensory and sympathetic neurons. The zinc finger transcription factor Klf7 interacts with an important cis element of the TrkA minimal enhancer and is coexpressed with TrkA in these neurons. We show that KIf7 binds to the endogenous TrkA minimal enhancer and can activate transcription from the TrkA minimal enhancer in a sequence-dependent manner. in KIf7(-/-) newborn mice, we find a significant reduction in sensory neurons due to increased apoptosis. The neuronal loss is restricted to nociceptive neurons that normally depend on TrkA for neurotrophic support, while other populations of somatosensory neurons appear normal. The reduction of TrkA expression in sensory neurons is a direct effect of KIf7 gene ablation, rather than a secondary effect of cell death. As a result, KIf7(-/-) mice have deficient response to noxious stimuli. Finally, removal of one TrkA allele exacerbates the loss of TrkA(+) neurons in KIf7(-/-) mice. Thus, KIf7 specifically regulates TrkA gene expression and is required for the development of a subset of nociceptive sensory neurons.