BICCN

Establishing Common Coordinate Framework for Quantitative Cell Census in Developing Mouse Brains

Brain development is characterized by a diverse set of cell types that are born and connected into rapidly growing, complex 3D structures across time. Quantitative understanding of cell type composition and distribution in different brain regions provides fundamental knowledge about the building blocks of the brain and serves as an essential baseline with which to assess changes that may occur in brain disorders. Common coordinate frameworks (CCF) provide an essential spatial context with which to understand cell type composition and 3D arrangement in the mouse brain. For the adult mouse brain, the Allen CCF currently serves as a standard atlas resource with which to map and integrate results from different studies. On the other hand, the lack of CCFs in developing mouse brains significantly impedes progress on quantitative spatiotemporal understanding of cell types during neurodevelopment. To address this deficiency, we have assembled a highly synergistic, multi-institutional team with complementary skill sets to create developmental CCFs with associated ontology and true 3D anatomical labels while also demonstrating the application of our CCFs by generating quantitative mappings of GABAergic neurons in the developing mouse brain. Toward this end, we will first utilize MRI and light sheet fluorescent microscopy (LSFM) to develop high-resolution developmental CCFs at seven different developmental time points (E11.5, E13.5, E15.5, E18.5, P4, P14, and P56) with different cellular features highlighted, including total cell density, myelination, and neurovasculature. Second, we will create fully3D anatomical labels for the CCFs based on cellular and gene expression information, and build a comprehensive ontology that will allow anatomical region changes to be linked across development and maturation. Lastly, we will generate a cellular-resolution quantitative map of GABAergic neuronal subtypes using tissue clearing and LSFM imaging in developing mouse brains. The successful completion of this project will enable a broad field of scientists to leverage modern brain mapping technologies more effectively in studying the developing mouse brain.  

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