The role of N-cadherin in neural stem cells

人类大脑是由一种叫做神经干细胞的特殊细胞池发育而来的。这些细胞在一生中分裂，产生新的神经细胞，在发育过程中大脑的生长和成年生活中的维持都是必需的。与此同时，干细胞不会枯竭，这是通过一种被称为“不对称分裂”的过程实现的，即由分裂的干细胞(子细胞)形成的两个细胞有不同的命运/一个成为神经细胞，而另一个仍然是干细胞，从而更新干细胞群体。显然，导致这些不对称分裂的机制对大脑的正确发展是绝对基础的，我们知道异常会导致儿童的智力低下综合征。我们还知道，细胞命运的不同是由两种机制实现的；第一，控制命运的特殊分子在细胞某一部分的准确位置(“命运决定因素”)；第二，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都只出现在两个子细胞中的一个细胞中。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。在这里，我们将询问一组名为钙粘附素的分子是否也与内部的命运决定因素和细胞分裂分子结合，并将它们保持在正确的位置。钙粘附素已知将神经干细胞在外部结合在一起，从而使它们保持在发育中的大脑中的正确位置。我们将通过分子生物学来改变钙粘附素在神经干细胞上的位置，使用大鼠大脑切片来模拟人脑，并使这些实验能够在组织培养中进行。然后，我们将看到分裂的神经干细胞会发生什么，从而证明或反驳我们的想法是这些钙粘附素的功能。由于全身干细胞使用非常相似的机制进行分裂，我们的结果不仅对于更好地了解大脑，而且对于干细胞可能在疾病后提供修复手段的其他组织也是有价值的。

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.