Migration and Differentiation of Enteric Neuron Precursors

肠壁内有数以百万计的神经细胞，它们控制着许多肠道功能，包括蠕动。在发育过程中，这些神经细胞是由从发育中的大脑迁移出来的细胞产生的，这些细胞首先进入胃。这些迁移细胞被称为神经嵴细胞。进入胃后，神经嵴细胞在胃肠道壁内迁移，直到到达远端（肛门）。在胚胎小鼠中，神经嵴细胞在整个小肠和大肠的定植需要4天以上，而在人类中，这个过程可能至少需要一周。神经嵴细胞在整个胃肠道中生长是至关重要的，因为缺乏神经嵴细胞的肠道区域无法发挥作用，肠道内容物在缺乏神经细胞的区域前积聚。这种情况在一些婴儿身上发现（先天性巨结肠病），它只能通过手术切除缺乏神经细胞的区域来治疗。因此，迁移的神经嵴细胞在整个胃肠道中定植是必不可少的。目前，关于神经嵴细胞迁移的控制机制知之甚少，以及a)肠壁内的特定分子对迁移是否重要，以及b)神经嵴细胞的迁移行为是否主要由神经嵴细胞本身调节。在这项研究中，我们将拍摄神经嵴细胞通过胚胎小鼠肠道迁移的延时图像，以确定对迁移重要的因素。当神经嵴细胞在整个肠道中生长后，它们会发育成不同类型的神经细胞。我们还将研究影响不同类型神经细胞发育的一些因素。

There are many millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called neural crest cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the entire small and large intestines by neural crest cells takes over 4 days, and in humans the process probably takes at least one week. It is essential that the neural crest cells colonise the entire gastrointestinal tract, since regions of intestine lacking neural crest cells (and hence nerve cells) cannot function and intestinal contents build up in front of the region lacking nerve cells. This condition is found in some babies (Hirschsprung's disease), and it can only be treated by surgically removing the region lacking nerve cells. It is therefore essential that migratory neural crest cells colonise the entire gastrointestinal tract. Currently, little is known about the mechanisms controlling the migration of neural crest cells, and whether a) particular molecules within the gut wall are important for migration, and-or b) the migratory behaviour of the neural crest cells is regulated mostly by the neural crest cells themselves. In this study we will take time-lapse images of neural crest cells migrating through the gut of embryonic mice to identify the factors that are important for the migration. After the neural crest cells have colonised the entire intestine, they develop into different types of nerve cells. We will also examine some of the factors affecting the development of different types of nerve cells.