LINEAGE ORIGIN OF SPINAL CORD CELL TYPE DIVERSITY

The complexity and specificity of movement in vertebrates is driven by a rich diversity of spinal motor and interneuron cell types. During development, eleven spinal cord progenitor domains generate an equivalent number of cardinal neuron types, each containing numerous motor and interneuron subpopulations. How progenitor domains, individual progenitors, and post-mitotic diversity relate to each other however is still unknown. Intrinsic and/or extrinsic factors could shape the identity and proportions of post-mitotic cells. We performed high-resolution single-progenitor lineage tracing in the embryonic mouse spinal cord using mosaic analysis with double markers (MADM). Our quantitative study of lineage progression revealed that nearly all spinal cord progenitors undergo highly variable numbers of proliferative, neurogenic, and gliogenic cell divisions. The nascent clonally-related neurons migrate radially over large distances, can span the dorsoventral axis, and even cross the spinal cord midline. Subsequent molecular and morphometric analysis confirms high levels of progenitor multipotency, with one progenitor capable of producing several molecularly and morphologically-distinct neuron types, as well as astrocytes. These findings redefine spinal cord development as a flexible process in which lineage variability—rather than rigid progenitor identity—drives the generation of cellular diversity.