Vadigepalli Rajanikanth, Hao Haiping, Miller Gregory M, Liu Hui, Schwaber James S
Department of Pathology, Anatomy and Cell Biology, Daniel Baugh Institute for Functional Genomics and Computational Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Neuroreport. 2006 Sep 18;17(13):1437-41. doi: 10.1097/01.wnr.0000227989.15422.71.
A significant functional role for epidermal growth factor receptor (EGFR) in the suprachiasmatic nucleus is suggested by recent findings that epidermal growth factor receptor and its ligand transforming growth factor-alpha are highly expressed in the suprachiasmatic nucleus. Recent studies indicate that epidermal growth factor receptor activation induces behavioral and physiological effects, strengthening the notion that epidermal growth factor receptor can modulate suprachiasmatic nucleus neural function and behavior. A global transcriptional profiling study is performed to investigate the gene expression response to epidermal growth factor receptor activation in the suprachiasmatic nucleus. The results indicate that all of the observed gene expression response is circadian-time dependent. The response included several genes encoding different neuropeptide receptors, ion channels and kinases. In order to hypothesize the transcription factors underlying the epidermal growth factor receptor response, different circadian-time-dependent gene expression groups were analyzed for enriched transcriptional regulatory elements in the promoters. The results indicate that several transcription factors such as Elk1 and cAMP-responsive element binding protein/activating transcription factor family, known to be 'input points' to the core clock network, are playing a role. Together, these results indicate that epidermal growth factor receptor has a circadian-time-dependent neuromodulatory function in the suprachiasmatic nucleus.
近期研究发现，表皮生长因子受体（EGFR）及其配体转化生长因子-α在视交叉上核中高表达，这提示了EGFR在视交叉上核中具有重要的功能作用。近期研究表明，EGFR激活可诱导行为和生理效应，强化了EGFR能够调节视交叉上核神经功能和行为的观点。开展了一项全基因组转录谱研究，以探究视交叉上核中对EGFR激活的基因表达反应。结果表明，所有观察到的基因表达反应均呈昼夜节律时间依赖性。该反应包括几个编码不同神经肽受体、离子通道和激酶的基因。为了推测EGFR反应背后的转录因子，对不同的昼夜节律时间依赖性基因表达组进行了分析，以寻找启动子中富集的转录调控元件。结果表明，几种转录因子，如已知为核心时钟网络“输入点”的Elk1和环磷酸腺苷反应元件结合蛋白/激活转录因子家族，正在发挥作用。总之，这些结果表明EGFR在视交叉上核中具有昼夜节律时间依赖性的神经调节功能。
