The role of N-cadherin in neural stem cells

人类的大脑是由一群叫做神经干细胞的特殊细胞发育而来的。这些细胞在人的一生中不断分裂，产生新的神经细胞，这些神经细胞在发育过程中为大脑的生长和成年后的维持所必需。同时，干细胞不会耗尽，这是通过一种称为“不对称分裂”的过程实现的，在这种过程中，由分裂的干细胞（子细胞）形成的两个细胞具有不同的命运/一个成为神经细胞，而另一个仍然是干细胞，从而更新干细胞群。很明显，导致这些不对称分裂的机制对于大脑的正确发育是绝对重要的，我们知道异常会导致儿童的智力迟钝综合症。我们还知道，细胞命运的差异是由两种机制实现的；首先，控制命运的特殊分子在细胞某一部分的精确位置（“命运决定因素”），其次，控制细胞在分裂过程中分裂的确切位置，以便这些命运决定因素最终只在两个子细胞中的一个中结束。然而，我们不知道这两种机制的细节，也不知道它们如何如此精确地定位命运决定因素和细胞分裂。​我们将利用分子生物学来改变钙粘蛋白在神经干细胞上的位置，用大鼠大脑切片来模拟人脑，使这些实验能够在组织培养中进行。然后我们会看到分裂的神经干细胞发生了什么，从而证明或反驳我们的想法是这些钙粘蛋白的功能。由于全身的干细胞使用非常相似的分裂机制，我们的结果不仅对更好地了解大脑，而且对干细胞可能提供疾病修复手段的其他组织有价值。

The human brain develops from a pool of special cells called neural stem cells. These cells divide throughout life, generating the new nerve cells required for the growth of the brain during development and for its maintenance in adult life. At the same time, the stem cells are not depleted, and this is achieved by a process called 'asymmetrical division', where the two cells formed by a dividing stem cell (daughter cells) have different fates / one becomes a nerve cell while the other remains a stem cell so renewing the stem cell population. Clearly, then, the mechanisms that enable these asymmetrical divisions are absolutely fundamental to the correct development of the brain, and we know that abnormalities cause mental retardation syndromes in children. We also know that the difference in cell fates is achieved by two mechanisms; first, the precise location to one part of the cell of special molecules that control fate ('fate determinants') and second, control of exactly where the cell splits apart during division so that these fate determinants all end up in only one of the two daughter cells. We don't know, however, the details of these two mechanisms and how they so precisely locate fate determinants and cell splitting. Here, we will ask whether a group of molecules called cadherins, known to stick the neural stem cells together on the outside so keeping them in the correct place in the developing brain, also bind to the fate determinants and cell-splitting molecules on the inside and keep them in the right place. We will do this by using molecular biology to alter the location of cadherins on the neural stem cells, using slices of rat brain to model the human brain and enable these experiments do be done in tissue culture. We will then see what happens to the dividing neural stem cells and so prove or disprove our ideas as the function of these cadherins. As stem cells throughout the body use quite similar mechanisms to divide, our results will be valuable not only for a better understanding of the brain but also for other tissues where stem cells might provide a means of repair following disease.