Multipotent progenitors instruct ontogeny of the superior colliculus.

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• The mammalian superior colliculus (SC) is crucial for multisensory integration.
• SC comprises diverse excitatory and inhibitory neurons and glia.
• Developmental principles of SC cell-type diversity remain unclear.

Purpose of the Study:

• Investigate the developmental mechanisms generating SC cell-type diversity.
• Determine the lineage potential of radial glial progenitors (RGPs) in the SC.
• Elucidate the role of PTEN in SC neurogenesis.

Main Methods:

• Employed genetic mosaic analysis with double markers (MADM)-based clonal analysis combined with single-cell sequencing (MADM-CloneSeq).
• Performed in silico and in vivo lineage tracing, preserving spatial information.
• Analyzed clonally related cell lineages.

Main Results:

• SC RGPs are exceptionally multipotent, capable of producing all SC neuron types.
• Individual RGPs can generate diverse neuronal fates even at terminal division.
• Neuronal type proportions are established in a PTEN-dependent manner, not by pre-defined clonal composition.

Conclusions:

• Established a foundational framework for mammalian SC ontogeny at the single-RGP/-cell level.
• Demonstrated the remarkable multipotency of SC RGPs.
• Highlighted the PTEN-dependent regulation of neuronal proportions in SC development.