LINEAGE SPECIFICATION OF NEURONAL PRECURSORS IN THE MOUSE SPINAL-CORD

We have investigated the differentiation potential of precursor cells within the developing spinal cord of mice and have shown that spinal c ord cells from embryonic day 10 specifically give rise to neurons when plated onto an astrocytic monolayer, Ast-1. These neurons had the mor phology of motor neurons and >83% expressed the motor neuron markers c holine acetyltransferase, peripherin, calcitonin gene-related peptide, and L-14. By comparison, <10% of the neurons arising on monolayers of other neural cell lines or 3T3 fibroblasts had motor neuron character istics. Cells derived from dorsal, intermediate, and ventral regions o f the spinal cord all behaved similarly and gave rise to motor neuron- like cells when plated onto Ast-1. By using cells that expressed the l acZ reporter gene, it was shown that >93% of cells present on the Ast- 1 monolayers were motor neuron-like. Time-lapse analysis revealed that the precursors on the Ast-1 monolayers gave rise to neurons either di rectly or following a single cell division. Together, these results in dicate that precursors in the murine spinal cord can be induced to dif ferentiate into the motor neuron phenotype by factors produced by Ast- 1 cells, suggesting that a similar factor(s) produced by cells akin to Ast-1 may regulate motor neuron differentiation in vivo.