In vivo analysis of the proliferative properties and morphological dynamics of radial glial cells in the Xenopus brain

我们的身体由数十亿个细胞组成，其中许多细胞都是高度专业化的，以执行不同的功能。在发育过程中，所有这些细胞都必须出生，很明显，一些细胞，被称为“干细胞”或“祖细胞”，可以通过连续分裂产生不同类型的细胞。了解哪些细胞起着祖细胞的作用，它们是如何被调节的，以及它们产生哪些类型的细胞，是我们理解身体发育的基础。此外，了解这些事件将揭示哪些过程在发育性疾病中变得异常，并有可能使我们能够在治疗上利用这些细胞。本研究计划在神经系统发育的背景下解决这些问题。在我们的大脑中有两大类细胞，可电兴奋的神经元和不可兴奋的神经胶质细胞。最初，人们认为这两个类在发育的早期就分化了，因此代表了不同的细胞家族或“谱系”。然而，最近的研究表明，在发育中的神经系统中有一种有趣的神经胶质细胞亚群，称为“放射状神经胶质细胞”，表现出祖细胞的特征，并可能产生我们大脑部分的大多数神经元。在这一系列的研究中，我们计划检查放射状胶质细胞在一个完整的，发育中的神经系统中的行为。使用非侵入性的高分辨率成像方法，我们将观察活体放射状胶质细胞的行为以及它们如何与未成熟大脑中的其他细胞进行交流。我们将探索放射状胶质细胞是否具有祖细胞的功能，并将追踪它们所产生的细胞类型的身份。最后，我们将研究放射状胶质细胞与其邻近细胞之间的持续通信是否对脑细胞分化为不同功能的方式很重要。我们预计这些实验将通过描述活脑细胞的出生和成熟过程，为发育生物学领域提供新颖而重要的数据。这项工作旨在提高我们对人类神经发育障碍的理解和治疗，它将使那些正在研究如何培养神经细胞以修复受损大脑的科学家受益。

Our bodies are made up of billions of cells, many of which are highly specialised in order to carry out different functions. During development all of these cells must be born and it is clear that some cells, referred to as 'stem' or 'progenitor' cells, can give birth to different types of cells by successively dividing. Understanding which cells function as progenitors, how they are regulated and what types of cells they give birth to, is fundamental to our understanding of how the body develops. Furthermore, understanding these events will reveal which processes become abnormal in developmental diseases and, potentially, will enable us to harness these cells therapeutically. This research proposal addresses these questions in the context of the developing nervous system. In our brains there are two major classes of cells, the electrically excitable neurons and the non-excitable glial cells. Originally it was believed that these two classes diverged very early during development and so represented different cell families or 'lineages'. However, recent work has indicated that an intriguing subset of glial cells in the developing nervous system, called 'radial glia', exhibit features of progenitor cells and may give birth to the majority of neurons in parts of our brains. In this series of studies we plan to examine the behaviour of radial glial cells in the context of an intact, developing nervous system. Using non-invasive, high-resolution imaging methods we will watch the behaviour of live radial glial cells and how they communicate with other cells in the immature brain. We will explore whether radial glia function as progenitor cells and will trace the identity of the types of cells that they give birth to. Finally, we will examine whether ongoing communication between radial glia and their neighbouring cells are important for the way brain cells become specialised for their different functions. We anticipate that these experiments will contribute novel and important data to the field of developmental biology by characterising the events surrounding the birth and maturation of cells in the living brain. The work aims to improve our understanding and treatment of neurodevelopmental disorders in humans, and it will benefit scientists that are investigating ways of growing nerve cells in order to repair damaged brains.