Myocyte enhancer factors-2B and-2C are required for adhesion related kinase repression of neuronal gonadotropin releasing hormone gene expression
Myocyte enhancer factors-2B and-2C are required for adhesion related kinase repression of neuronal gonadotropin releasing hormone gene expression
复制标题
DOI：
10.1074/jbc.m007097200
复制
发表时间：
2000-12-15
影响因子：
4.8
通讯作者：
Wierman, ME
中科院分区：
文献类型：
--
作者：
Allen, MP;Xu, M;Wierman, ME
合成下丘脑肽，促性腺激素释放激素(GnRH)对生殖功能至关重要。促性腺激素释放激素神经元起源于嗅觉区，并在发育过程中迁移到前脑。最近，我们根据黏附相关激酶(ARK)在两个GnRH产生细胞系GT1-7和Gn10中的差异表达，将其与GnRH神经元的发育有关。方舟膜受体编码一个类似于细胞黏附分子的胞外区和一个胞内酪氨酸激酶。ARK在来自迁移的GnRH神经元的Gn10细胞中表达，但在迁移后表型的GT1-7细胞中不表达。在这里，我们发现Ark和GnRH转录本在妊娠中期共同定位于筛板，这表明Ark在体内迁移的GnRH神经元中表达。此外，我们还发现GnRH基因是ARK信号的下游靶点。ARK通过肌细胞增强因子-2B和-2C(MEF-2B和-2C)与近端大鼠GnRH：启动子内的同源蛋白的协调结合来抑制GnRH神经细胞中GnRH基因的表达。鉴于MEF-2蛋白在大脑中广泛表达，这些研究为MEF-2在神经元发育过程中的作用提供了进一步的证据。此外，我们的研究阐明了Ark在GnRH神经元迁移过程中调节GnRH基因表达的潜在作用。
Synthesis of the hypothalamic peptide, gonadotropin releasing hormone (GnRH), is paramount for reproductive function. GnRH neurons originate in the olfactory region and migrate into the forebrain during development. We recently implicated adhesion related kinase (Ark) in GnRH neuron development based on its differential expression in two GnRH producing cell lines, GT1-7 and Gn10. The Ark membrane receptor encodes an extracellular domain resembling cell adhesion molecules and an intracellular tyrosine kinase. Ark is expressed in Gn10 cells derived from migrating GnRH neurons but not GT1-7 cells of the post-migratory phenotype. Here, we show that Ark and GnRH transcripts are colocalized in the cribriform plate at midgestation, suggesting that Ark is expressed in migrating GnRH neurons in vivo. Furthermore, we have identified the GnRH gene as a downstream target of Ark signaling. Ark inhibits GnRH gene expression in GnRH neuronal cells via the coordinated binding of myocyte enhancer factor-2B and -2C (MEF-2B and -2C) and a putative homeoprotein within the proximal rat GnRH: promoter. Given that MEF-2 proteins are widely expressed in the brain, these studies provide further evidence for MEF-2 action during neuronal development. Moreover, our studies elucidate a potential role for Ark in regulating GnRH gene expression during GnRH neuronal migration.