IN VITRO MODEL DEVELOPMENT OF SEROTONIN NEURONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们寻求一种5-羟色胺神经元的体外灵长类动物模型。利用恒河猴胚胎干细胞系366.4，开发了一种通过免疫细胞化学检测色氨酸羟基酶和5-羟色胺再摄取转运蛋白来产生高比例5-羟色胺神经元的方法。此外，胚胎干细胞来源的神经元表达雌激素受体β(ERbeta)和孕激素受体(PR)的方式类似于猕猴大脑中的5-羟色胺神经元。我们现在试图描述这些神经元的生理功能，并检测在分化的每个阶段的基因表达谱。这种培养系统将减少我们对灵长类动物的需求，并使目前尚不可行的灵长类5-羟色胺系统的细胞和分子研究成为可能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We sought an in vitro primate model for serotonin neurons. Using the rhesus embryonic stem cell (ESC) line 366.4, a protocol was developed which generates a high percentage of serotonin neurons as determined by immunocytochemistry for tryptophan hydroxylase and the serotonin reuptake transporter. In addition, the ESC-derived neurons express estrogen receptor beta (ERbeta) and progesterone receptors (PR) in a manner similar to serotonin neurons in the macaque brain. We now seek to characterize physiological functions of these neurons and to examine the gene expression profile during each stage of differentiation. This culture system will reduce our need for primates and enable cellular and molecular studies of the primate serotonin system that are not currently feasible.