Multipotent progenitors instruct ontogeny of the superior colliculus

The superior colliculus (SC) is a dorsal midbrain structure known for its roles in multisensory integration and motor responses and its dysfunction has been linked to neurodevelopmental diseases. SC is a highly organized structure composed of distinct laminae of diverse neuronal and glial cell types. However, the precise developmental principles instructing the generation of SC cell-type diversity are still unknown. To investigate this, we pursued lineage tracing using genetic MADM (Mosaic Analysis with Double Markers)-based clonal analysis with single cell sequencing (MADM-CloneSeq) and in silico reconstruction. Our analysis revealed that individual SC progenitors are exceptionally multipotent with the capacity to produce all known excitatory and inhibitory SC neuron types throughout neurogenesis. We also identified an essential role of PTEN signaling in establishing appropriate proportions of cell type abundance. In conclusion, our work provides a novel framework for the emergence of cell-type diversity and ontogeny in the SC.