Mash1 Defines Lineage Restricted Neuronal and Oligodendrocytic Precursor Cells in Spinal Cord Development

Recent advances have defined distinct neural progenitor and early interneuron pools in the developing spinal cord and the molecular events that influence progenitor cell fate. However, these early neurons have not been traced to adult neuron types. The transcription factor Mash1 is transiently expressed in a subset of neural progenitors and possesses a pro-neural function. The transient nature of its expression limits the ability to trace Mash1+ progenitors. To study the developing neural tube from progenitor to adult neuron, transgenic mouse strains were generated that express GFP, Cre recombinase, and tamoxifen-inducible Cre recombinase. The M1-GIC mouse line, showed faithful Mash1 expression recapitulation and traces Mash1+ progenitors mainly to dI3 and dI5 interneurons. This supports data from the Mash1 null mutant where these populations are decreased or absent. Using M1-GIC;R26R-lacZ mice, I was able to trace Mash1 expressing cells to neurons and oligodendrocytes in the adult mouse, but tracing to astrocytes was never observed. These data refute the conventional understanding that Mash1 is purely pro-neuronal, and is consistent with recent findings of Mash1 descendents in the early postnatal subventricular zone. Using M1-CRE-ER™;R26RlacZ and M1-CRE-ER™;R26R-YFP, Mash1+ cells trace into adulthood in a temporally-dependant manner. Cells expressing Mash1 at E10.5 become neurons of the dorsal horn in lamina I-IV while cells expressing Mash1 at E15.5 become oligodendrocytes spread over both gray and white matter. As a control, Nestin- CreERT2;R26R-lacZ and Nestin-CreERT2;R26R-YFP mice were used to confirm that common progenitors of all neural cell types can be traced from E10.5 to P21. This data provides evidence that Mash1 defines lineage restricted precursors that exit the cell cycle rapidly, and Mash1 is necessary for efficient loss of common progenitor characteristics as seen in the Mash1 null mutant. This data refines our understanding of progenitor characteristics and Mash1 function in the developing spinal cord.