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Single embryonic and adult neural stem cells (NSCs) are characterized by their self-renewal and differentiation potential. Lineage tracing via clonal analysis allows for specific labeling of a single NSC and tracking of its progeny throughout development. Over the past five decades, a plethora of clonal analysis methods have been developed in tandem with integration of chemical, genetic, imaging and sequencing techniques. Applications of these approaches have gained diverse insights into the heterogeneous behavior of NSCs, lineage relationships between cells, molecular regulation of fate specification and ontogeny of complex neural tissues. In this review, we summarize the history and methods of clonal analysis as well as highlight key findings revealed by single-cell lineage tracking of stem cells in developing and adult brains across different animal models.

Illumination of neural development by in vivo clonal analysis