The development of functional tissues requires precise spatial and temporal control of cell fate specification. Using the vertebrate spinal cord as a model system, we investigate how these regulatory principles generate the cellular diversity needed for circuit assembly. While its molecular patterning is well characterised, how the spatial and temporal axes constrain lineage trajectories has remained unclear. To address this, we combined genomic barcoding with single-cell RNA sequencing in chick and human embryos to generate cell-type-resolved clonal maps of the spinal cord. We found that neurogenesis follows a hierarchical organisation: the neural tube first partitions into five broad lineage subdivisions, which later resolve into the eleven classical progenitor domains that generate the major neuronal classes. This bifurcating architecture supports a model of sequential binary fate decisions. The most prominent lineage restriction occurs at the alar-basal boundary, separating sensory-processing from motor-control circuits. Individual progenitors can generate neurons across multiple temporal waves while remaining constrained within their lineage subdivision, demonstrating persistence of spatial identity despite temporal competence changes. Among sensory populations, we identify two distinct developmental routes to pain- and itch-processing interneurons. These principles are conserved in human embryos, where most neuronal fate decisions are resolved by six weeks post-conception. Together, our findings provide a framework for understanding how lineage architecture shapes tissue complexity and reveal modular compartmentalisation as a conserved strategy in neural development and evolution.

The talk is based on our very recent preprint, available here:

https://www.biorxiv.org/content/10.1101/2025.10.24.684328v1.full