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

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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.