The functions of the transcription factor Pax6 in thalamic neuronal specification and axonogenesis

在这项研究中，我们试图发现为什么一个叫做Pax6的基因对大脑中一个叫做丘脑的关键部分的正常生长如此重要。丘脑对于我们感知周围世界的能力至关重要，因为它通过大脑将触觉，温度，疼痛，视觉，听觉等信息传递到大脑皮层。Pax6基因编码一种蛋白质，该蛋白质通过与DNA结合来影响其他基因的活性，从而对发育进行高水平控制。它在小鼠和人类中是相同的，当它被阻止工作时，丘脑变得严重异常：它太小了，它的细胞含有一些错误的分子，它无法与大脑皮层进行正常连接。我们仍然不知道这些是否是所有的缺陷，我们也不知道它们为什么会发展。要获得详细的答案，特别是对这些问题中的第二个问题，将需要很长时间，我们计划在这里迈出第一步。我们设计了实验来比较正常小鼠和各种类型的Pax6突变体中丘脑形成时发生的所有主要事件，以寻找Pax6水平降低或升高时的缺陷。我们将研究丘脑细胞的产生，细胞与邻近组织的交换，丘脑细胞产生的分子以及丘脑与大脑皮层的联系。当我们表明Pax6是一个特定过程所必需的时，我们将测试这种需要是否是因为Pax6通常在显示异常的细胞内起作用。一些缺陷可能是其他细胞中Pax6水平变化的连锁效应，然后与显示异常的细胞发生不正确的相互作用。为了找到缺陷的来源，我们将只改变特定细胞中Pax6的表达，而不改变其他细胞。未来的工作将建立在这里获得的结果：我们希望通过找出哪些丘脑细胞需要Pax6的事件，我们将能够设计进一步的实验，发现Pax6的生物化学？在这些细胞中的行为。

In this research we are trying to discover why a single gene called Pax6 is so important for the normal growth of a critical part of the brain called the thalamus. The thalamus is essential for our ability to perceive the world around us since it transmits information about touch, temperature, pain, vision, hearing and so on through the brain to the cerebral cortex. The Pax6 gene codes for a protein that exerts high-level control of development by affecting the activity of other genes by binding to DNA. It is identical in mice and humans and when it is prevented from working the thalamus becomes seriously abnormal: it is too small, its cells contain some of the wrong molecules and it fails to make normal connections with the cerebral cortex. We still do not know if these are all of the defects and we do not know why they develop. Obtaining detailed answers particularly to the second of these questions will take a long time and here we plan to take a first step. We have designed experiments to compare all the major events that occur as the thalamus forms in normal mice and in Pax6 mutants of various types, to look for defects when Pax6 levels are lowered or raised. We shall examine thalamic cell production, the exchange of cells with adjacent tissue, molecules produced by thalamic cells and thalamic connections with the cerebral cortex. Where we show that Pax6 is needed for a particular process, we shall test whether the need is because Pax6 normally acts within the cells that show abnormalities. It is possible that some defects might be knock-on effects of changing Pax6 levels in other cells that then interact incorrectly with the cells showing abnormalities. To home in on the source of the defects we shall alter expression of Pax6 in specific sets of cells only, leaving others intact. Future work will build on results obtained here: we expect that by finding out which thalamic cells need Pax6 for which events we will be able to design further experiments to discover the biochemistry of Pax6?s actions within those cells.