BICCN

Mapping Developmental Lineage Relationships in the Cerebral Cortex

This project seeks to utilize novel lineage tracing technologies to explore the developmental origins of the brain at the level of individual cell types and distinct functional areas. To investigate these developmental relationships, the Nowakowski lab will implement a suite of high-throughput lineage tracing tools. In the first approach, relationships between distinct cellular subtypes in the brain will be explored using highly diverse DNA barcodes to identify whether or not they are born from distinct progenitors. Lineage relationships will be combined with single-cell transcriptomic analyses to determine both the developmental identity and the terminal fate of the cells. Temporal relationships between cell types that share a lineage history will also be investigated using dynamic, continuously editing barcodes. In the second goal of this project, developmental trajectories will be mapped to and contexualized with their spatial identity. This will enable a clear understanding of how developmentally-related cells are organized within the cortex and across distinct functional areas by employing novel in-situ sequencing techniques that allow for a spatial readout of lineage history. This project will build on existing knowledge of the vast diversity of cell types and functions in the mature cortex and provide a developmental perspective on how these cells arise and organize themselves during development, filling in an essential gap in knowledge that currently exists between the two fields. The technologies generated and utilized in this project will provide widely-applicable tools for a range of developmental questions that will allow for characterization of lineage relationships at scales ranging from the whole brain to individual cells.

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