Neural stem cell fate decisions: clonal and spatially-resolved approaches.

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The brain is a highly complex tissue that is made up of billions of cells and trillions of connections. Stem cells found in the brain, referred to as neural stem cells, are tasked with producing all of the appropriate cell types (such as neurons), at the right times and in the right numbers to ensure the brain is assembled correctly during development. Understanding how neural stem cells in the embryonic brain differentiate into all of the cells which make up the brain has been hampered by our previous inability to follow these stem cells one cell at a time. While molecules found inside neural stem cells have indisputable roles in the differentiation of these cell towards their progeny cell types, much less is know with respect to the interactions between neural stem cells and neighboring cells and how this may impact the differentiation of neural stem cells. Such interactions between cells (known as cell-cell interactions) are known to activate molecular cascades insides neural stem cells that lead to the expression of genes which could control the types and number of daughter cells that neural stem cells can produce. My research program aims to build a detailed model of how single neural stem cells in the embryonic brain give rise to all of their progeny cell types late in gestation and reveal the roles played by cell-cell interactions in these processes. This model will not only capture neural stem cell behavior in time (as the brain develops) but also place these events in a spatial context in precise locations in the brain. To do this, we will develop methods which will allow use to track, in a highly parallel manner, the progeny cells produced from single neural stem cells during development. We will then use the data produced from this approach to build a detailed model of neural stem cell differentiation during development. Subsequently, we will use new and existing methods to understand cell-cell interactions in a spatially-resolved manner and assess the functions of these interactions in the differentiation of neural stem cells. Collectively, these studies will enable us to understand how single stem cells produce all of the progeny cell types needed to build a tissue during development.