Tracing cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics

The cerebral cortex comprises diverse neuron and glial cell types generated by radial glial progenitors (RGPs) during development. Although RGPs broadly differentiate according to temporally and spatially regulated molecular logics, the lineage hierarchies linking individual progenitors to defined cell (sub)types are not well understood. Clone-resolved transcriptomics, combining molecular barcoding and single-cell RNA sequencing, allow high-resolution lineage tracing at the single-clone/cell level across different species and models. In this mini-review, we synthesize recent advances in this field, uncovering unexpected lineage relationships in the developing brain, with a particular focus on the cerebral cortex. We further highlight new insights into species-specific differences in the developmental programs generating cell-type diversity, linking changes in clonal architecture to lineage diversification during cortical evolution.