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Genetic regulation of neural stem/progenitor cells and neurogenesis in the adult hypothalamus

成人下丘脑神经干/祖细胞和神经发生的遗传调控

基本信息

批准号：
BB/L003406/1
负责人：
Mohammad Hajihosseini
金额：
$ 56.67万
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FL003406%2F1
关键词：
Genetic regulation neural stem progenitor

项目摘要

The hypothalamus is an area of the brain that regulates key physiological functions ranging from mood and sleep to appetite and energy expenditure. Recent work from our lab has shown that new neurons are generated in the hypothalamus of adolescent and adult mice. Intriguingly, these neurons appear to be destined for circuits that regulate appetite and energy expenditure. This raises the interesting possibility that these circuits can be modulated to the benefit of human health. In particular, to preserve the healthy functioning of the brain in aged individuals and tackling eating disorders, such as obesity.We have discovered that the new hypothalamic neurons arise from a unique population of stem cells, called tanycytes. We have also found that these cells express a very important signaling gene, called Fgf10. Our main objectives are to characterize and understand the function/s of Fgf10 in tanycytes. To meet these objectives, we will use well-characterized tissue culture systems and examine the brains of genetically modified mice, in which the functioning of Fgf10 has been abrogated or elevated. We will also investigate the cohort of genes and molecules that Fgf10 may talk to and interact with to exert its functions. The generated information will advance our knowledge of brain stem cells and brain function and may well lead to the development of molecular tools to positively modulate brain function.

下丘脑是大脑的一个区域，负责调节从情绪和睡眠到食欲和能量消耗的关键生理功能。我们实验室最近的工作表明，在青春期和成年小鼠的下丘脑中产生了新的神经元。有趣的是，这些神经元似乎注定是调节食欲和能量消耗的回路。这提出了一种有趣的可能性，即这些回路可以被调节以造福人类健康。特别是，为了保持老年人大脑的健康功能，并解决饮食失调，如肥胖。我们已经发现，新的下丘脑神经元来自一个独特的干细胞群，称为tanycells。我们还发现这些细胞表达一种非常重要的信号基因，称为Fgf10。我们的主要目标是表征和理解Fgf10在伸长细胞中的功能。为了实现这些目标，我们将使用特征良好的组织培养系统，并检查转基因小鼠的大脑，其中FGF10的功能已被废除或升高。我们还将研究Fgf10可能与之交谈并相互作用以发挥其功能的基因和分子。所产生的信息将促进我们对脑干细胞和脑功能的了解，并可能导致积极调节脑功能的分子工具的发展。