GDNF and development of the intestinal nervous system

动物模型显示，肠道在出生时很短，但在年轻的成年后可以达到几英尺长。在生长中的肠道中，平滑肌细胞数量增加，负责收缩或松弛，这将推动肠道内容物适当地消化和吸收营养。这些细胞需要控制肠道神经系统中数以百万计的神经元才能做到这一点。这些神经元在出生时就存在，数量不会增加，但就像大脑或脊髓中的神经元一样，它们必须延伸出细长的突起（轴突），通过释放一种叫做神经递质的化学物质来作用于其他细胞。与正在学习科学方法的宝贵技能的学生一起工作，我将研究他们如何以及为什么在生长中的肠道中这样做。我们将一起研究保持这群神经细胞存活的因素，以及导致它们将轴突延伸到正确位置的因素。在胚胎早期，早在出生前，研究表明，神经元通过以下因素进入将成为肠道的管道。它们被称为神经营养因子，只有当目标细胞产生能够检测到它们的正确分子时，它们才能影响目标细胞。我们将研究这些相同的因素是否在出生后继续由肠壁细胞产生，以及神经元是否继续能够对它们作出反应。主要的神经营养因子是神经胶质细胞系衍生的神经营养因子（GDNF），因为它最初是在神经胶质细胞中发现的，但现在已知它是由其他类型的细胞产生的。我们将研究它是如何以及何时产生的，以及如何通过组织培养来影响神经元，这只是一种将细胞保存在体外以供观察和操作的方法。这可能揭示了生长中的肠道是如何确保其至关重要的神经系统与它一起“生长”的——不断改变其线路以能够控制对肠道功能如此重要的肌肉细胞。这个项目将增加我们对自然世界的认识，增加加拿大知识型劳动力，为许多领域的研究工作提供技术支持，并培养可能继续在学术界或工业界工作的研究生。

Animal models show that the intestine is quite short at birth, but reaches several feet in length in the young adult. In the growing intestine, smooth muscle cells increase in number and are responsible for contraction or relaxation that will propel the intestinal contents appropriately for digestion and absorption of nutrients. These cells require the control of the millions of neurons in the intestinal nervous system in order to do this. These neurons are present at birth and do not increase in number at all, but like neurons in the brain or spinal cord, they must extend long thin processes (axons) to act on other cells by the release of chemicals called neurotransmitters. Working with students that are learning valuable skills in scientific methods, I will study how and why do they do this in the growing intestine. Together, we will investigate the factors that keep this population of nerve cells alive, and that cause them to extend their axons to the right places. In the early embryo, long before birth, studies show that the neurons enter the tube that would become the intestine through following factors that it was making. Called neurotrophins, these can influence target cells only when they make the right molecules that can detect them. We will study whether these same factors continue to be made after birth, by cells in the intestinal wall, and whether neurons continue to be able to respond to them. The major neurotrophin is glia cell line derived neurotrophic factor (or GDNF) since it was first found in glial cells, but is now known to be made by other cell types. We will study how and when it is made, and how affects neurons through use of tissue culture, which is simply a way of keeping cells outside the body for observation and manipulation. This could reveal how the growing intestine makes sure that its vitally important nervous system "grows" right along with it - constantly changing its wiring to be able to control the muscle cells that are so important to intestinal function. This project will increase our knowledge of the natural world, and add to Canada's knowledge-based work force, providing technologists for support of research endevours in many areas and training graduate students that may continue in academia or in industry.