About Reza Kalhor's Work
Perturbations in embryonic development that affect a subset of cells at one stage can start domino effects that end in complex phenotypes. Understanding these domino effects requires the ability to map mammalian development. I propose a whole-organism genetic barcoding platform for mapping detailed developmental lineage trees in mammals. In this platform, we will engineer mice to record each cell’s lineage in its genome in the form of DNA barcodes. We will establish in situ sequencing strategies to extract these barcodes together with single-cell transcriptomes directly from tissues. We will also develop computational strategies for reconstructing developmental histories using cell barcode and identity information. We will apply this platform to investigate how certain gene mutations alter embryogenesis to result in neurodevelopmental anomalies. These approaches will transform our understanding of how genetic factors affect mammalian development and how congenital anomalies emerge.