Role of distinct cortical progenitor subtypes in cortical neuronal and glial subtype specification

我们大脑中最大的结构是大脑皮层，它负责处理高级认知、运动和感觉任务的信息。它由许多不同类型的细胞组成，这些细胞是在子宫早期大脑发育期间由几个母干细胞（称为祖细胞）形成的。这些不同类型的细胞，例如皮质神经元和神经胶质，都有一个谱系——一个可以追溯其历史和起源的家谱。有研究表明，具有共同谱系的姐妹神经元优先相互连接，最终形成回路，而不是与来自其他祖细胞和不同谱系的神经元建立连接。接下来要回答的问题是：所有的母祖细胞都能产生相同的姊妹神经元集吗？还是存在不同类型的母细胞并产生不同的姊妹神经元？如果是第一种情况，神经元将在对所经历的刺激作出反应时获得其独特的特征。另一方面，第二种情况意味着姐妹神经元群的身份是基因预先决定的。虽然目前的观点认为皮质祖细胞可以产生任何类型的神经元，但人们普遍认为几种不同的祖细胞亚型在发育过程中共存。在我们的工作中，我们重点研究了祖细胞的两个亚型，它们具有许多共同的特征，但可以通过它们的长或短形态特征来区分。由于缺乏分子和遗传工具来分别研究这两种亚型，我们还不知道它们是否真的是不同的祖细胞亚型，产生不同的神经元和胶质类型。我们工作的目标是揭示这两种母细胞类型的不同能力。揭示由每个祖细胞亚型产生的神经元和神经胶质亚型将使我们深入了解来自不同母祖细胞的神经元回路的“构建块”的独特组成。由于我们大脑中的微电路被认为是信息处理单元，了解它们的组件共享的共同起源可能会揭示以前隐藏的神经元布线原理。最近对发育中的胎儿大脑遗传变异的分析表明，一些遗传变异会对发育困难的风险产生重大影响，这说明了理解导致大脑发育过程中变异的机制的重要性。我们对神经元和神经胶质谱系对大脑发育的影响的研究将帮助我们更准确地了解大脑是如何发育的。只有通过这样的理解，我们才能开始了解当我们的大脑不以正常的方式发育时，到底是什么出了问题。

The largest structure in our brain is the cerebral cortex, which is responsible for processing information for higher cognitive, motor and sensory tasks. It comprises many different cell types which are made from a few mother stem cells, called progenitors, during early brain development in the womb. These different cell types, cortical neurons and glia, for example, have a lineage - a family tree tracing their history and origins. It has been suggested that sister neurons with a common lineage connect preferentially to each other, eventually forming circuits, rather than make connections with neurons from other progenitors and different lineages. The question to be answered is then: Can all mother progenitors generate the same sister neuron sets? Or do different types of mother cells exist and give rise to different sister neurons? If the first is the case, neurons will acquire their unique features in response to stimuli experienced. On the other hand, the second case implies that the identity of the sister neuronal groups are pre-determined genetically. Although the current opinion is that cortical progenitors can generate any neuron type, it is widely accepted that several different progenitor subtypes co-exist during development. In our work, we focus on two subtypes of progenitors, which share many features but are distinguishable by their long or short morphological features. Due to the lack of molecular and genetic tools to study these two subtypes separately, we do not yet know whether these are truly different progenitor subtypes generating distinct sets of neuronal and glial types.The goal of our work is to uncover the different competencies of these two mother cell types. Uncovering the neuronal and glial subtypes resulting from each progenitor subtype will give us an insight into the unique composition of the "building blocks" of neuronal circuits from different mother progenitors. Since microcircuits in our brain are thought to function as information processing units, understanding the common origins of their components sharing may reveal previously hidden principles of neuronal wiring. A recent analysis of genetic variation in the developing foetal brain has shown that some genetic variations can have a substantial impact upon risk for developmental difficulties, illustrating the importance of understanding the mechanisms that lead to variation during brain development. Our work on the impact of neuronal and glial lineages on brain development will help us to understand more about precisely how our brains develop. It is only through understanding development like this that we can begin to learn what is going wrong when our brains do not develop in the normal way.