HOMEOPROTEIN AND NEUROENDOCRINE PHENOTYPE

描述：定义细胞专一性的关键事件之一 神经内分泌组织的功能是神经递质的特性 在给定的单元格中表达。控制生命周期的分子事件 神经递质表型的选择受环境影响 刺激物。最终，细胞表型是由相互作用决定的。 具有调控元件的功能不同的转录因子 编码神经递质或神经递质生物合成的基因 酵素。本应用程序的重点是描述一种转录 与多巴胺b的调节区相互作用的因子 羟化酶(DBH)基因。DBH催化合成去甲肾上腺素， 仅在交感神经元、肾上腺嗜铬细胞中表达 以及某些脑核。申请人已为此克隆了一个cdna。 转录因子，命名为Arix，携带一个同源盒，并具有 发现Arix mRNA在去甲肾上腺素能组织中选择性表达 和细胞系。这些观察表明，Arix可能扮演着一个 在确定去甲肾上腺素能表型中的决定性作用 活着。这项建议的主要目标是了解 ARIX在调节去甲肾上腺素能表型中的作用。这一目标将 通过以下方式实现：(1)确定Arix在大鼠体内的表达模式 胚胎和出生后的外周和中枢神经系统 开发；(2)鉴定含Arix的分子成分 DNA-蛋白质复合体，以及(3)灭活Arix活性 儿茶酚胺能细胞系。这些研究的结果应该导致 交感肾上腺正常发育的再认识 表型，以及发育失败的后果 继续吧。此外，Arix基因可能被证明是一个因素 遗传性疾病的特征是 神经内分泌细胞。

DESCRIPTION: One of the key events defining the specificity of cell function in neuroendocrine tissues is the identity of neurotransmitter expressed in a given cell. The molecular events that control the selection of neurotransmitter phenotype are influenced by environmental stimuli. Ultimately, cellular phenotype is determined by the interaction of functionally distinct transcription factors with regulatory elements of genes that encode neurotransmitters or neurotransmitter biosynthetic enzymes. This application is focused on characterizing a transcription factor that interacts with the regulatory region of the dopamine b hydroxylase (DBH) gene. DBH catalyzes the synthesis of norepinephrine, and is expressed only in sympathetic neurons, adrenal chromaffin cells and certain brain nuclei. The applicant has cloned a cDNA for this transcription factor, designated Arix, which carries a homeobox, and has found that Arix mRNA is selectively expressed in noradrenergic tissues and cell lines. These observations suggest that Arix may play a definitive role in the determination of the noradrenergic phenotype in vivo. The main objective of this proposal is to understand the potential role of Arix in regulating the noradrenergic phenotype. This goal will be achieved by: (1) defining the pattern of Arix expression in the rat peripheral and central nervous system during embryonic and postnatal development; (2) identifying the molecular components of Arix-containing DNA-protein complexes, and (3) inactivating Arix activity in a catecholaminergic cell line. The results of these studies should lead to further understanding of the normal development of the sympathoadrenal phenotype, as well as the consequences of a failure of development to proceed. In addition, the Arix gene may prove to be a factor in inherited diseases characterized by the aberrant development of neuroendocrine cells.