Failure of spinal cord oligodendrocyte development in mice lacking neuregulin

Oligodendrocytes develop from a subpopulation of precursor cells within the ventral ventricular zone of the spinal cord. The molecular cues that direc t this spatially and temporally restricted event seem to originate in part from structures ventral to and within the spinal cord. Here, we present evi dence that the family of ligands termed neuregulins are necessary for the n ormal generation of mouse spinal cord oligodendrocytes. Oligodendrocytes ma ture in spinal cord explants from wild-type mice and mice heterozygotic for a null mutation in the neuregulin gene (NRG +/-) in a temporal sequence of developmental events that replicates that observed in vivo. However, in sp inal cord explants derived from mice lacking neuregulin (NRG -/-), oligoden drocytes fail to develop, Addition of recombinant neuregulin to spinal cord explants from NRG -/- mice rescues oligodendrocyte development. In wild-ty pe spinal cord explants, inhibitors of neuregulin mimic the inhibition of o ligodendrocyte development that occurs in NRG -/- explants, In embryonic mo use spinal cord, neuregulins are present in motor neurons and the ventral v entricular zone where they likely exert their influence on early oligodendr ocyte precursor cells.