The role of N-cadherin in neural stem cells

N-钙粘蛋白在神经干细胞中的作用

• 批准号: BB/L00402X/1
• 负责人: Charles Ffrench-Constant
• 金额: $ 15.65万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL00402X%2F1
• 关键词: role; cadherin; neural; stem; cells

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.

人类的大脑是由一群称为神经干细胞的特殊细胞发育而来的。这些细胞在整个生命过程中分裂，产生新的神经细胞，这些神经细胞是大脑在发育过程中生长和成年后维持所需的。与此同时，干细胞不会被耗尽，这是通过一个称为“不对称分裂”的过程实现的，其中由分裂的干细胞（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，从而更新干细胞群体。因此，很明显，这些不对称分裂的机制对大脑的正确发育至关重要，我们知道异常会导致儿童智力迟钝综合征。我们还知道，细胞命运的差异是通过两种机制实现的;第一，控制命运的特殊分子（“命运决定因素”）在细胞的一个部分的精确位置;第二，控制细胞分裂期间分裂的确切位置，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，也不知道它们是如何如此精确地定位命运决定因素和细胞分裂的。在这里，我们将询问一组称为钙粘蛋白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。已知钙粘蛋白在外部将神经干细胞粘在一起，使它们保持在发育中的大脑中的正确位置。我们将通过使用分子生物学来改变神经干细胞上钙粘蛋白的位置，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完成。然后，我们将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作为这些钙粘蛋白的功能。由于整个身体的干细胞使用非常相似的机制进行分裂，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后修复手段的其他组织都很有价值。

项目成果

Extracellular Matrix Regulation of Stem Cell Behavior.

干细胞行为的细胞外基质调节。

• DOI: 10.1007/s40778-016-0056-2
• 发表时间: 2016
• 期刊: Current stem cell reports
• 影响因子: 1.4
• 作者: Ahmed M;Ffrench-Constant C
• 通讯作者: Ffrench-Constant C

Disc1 variation leads to specific alterations in adult neurogenesis.

• DOI: 10.1371/journal.pone.0108088
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Chandran JS;Kazanis I;Clapcote SJ;Ogawa F;Millar JK;Porteous DJ;Ffrench-Constant C
• 通讯作者: Ffrench-Constant C

Neural stem cell quiescence comes to an un-sticky end.

神经干细胞静止期结束了。

• DOI: 10.1038/ncb3003
• 发表时间: 2014
• 期刊: Nature cell biology
• 影响因子: 21.3
• 作者: Long KR

The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation.

• DOI: 10.1016/j.stemcr.2018.07.014
• 发表时间: 2018-09-11
• 期刊: Stem cell reports
• 影响因子: 5.9
• 作者: Gyllborg D;Ahmed M;Toledo EM;Theofilopoulos S;Yang S;Ffrench-Constant C;Arenas E
• 通讯作者: Arenas E

Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin.

• DOI: 10.1038/ncomms10354
• 发表时间: 2016-02-03
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Long K;Moss L;Laursen L;Boulter L;Ffrench-Constant C
• 通讯作者: Ffrench-Constant C