LYSOPHOSPHATIDIC ACID RECEPTOR GENE VZG-1 LP(A1)/EDG-2 IS EXPRESSED BY MATURE OLIGODENDROCYTES DURING MYELINATION IN THE POSTNATAL MURINE BRAIN/

The growth-factor-like phospholipid lysophosphatidic acid (LPA) mediat es a wide variety of biological functions. We recently reported the cl oning of the first G-protein-coupled receptor for LPA, called ventricu lar zone gene-1 (vzg-1/lp(A1)/edg-2) because its embryonic central ner vous system (CNS) expression is restricted to the neocortical ventricu lar zone (Hecht et al. [1996] J. Cell Biol. 135:1071-1083). Vzg-1 neur al expression diminishes at the end of the cortical neurogenetic perio d, just before birth. Here, we have investigated the subsequent reappe arance of vzg-1 expression in the postnatal murine brain, by using in situ hybridization and northern blot analyses. Vzg-1 expression was un detectable by in situ hybridization at birth, but reappeared in the hi ndbrain during the 1st postnatal week. Subsequently, expression expand ed from caudal to rostral, with peak expression observed around postna tal day 18. At all postnatal ages, vzg-1 expression was concentrated i n and around developing white matter tracts, and its expansion, peak, and subsequent downregulation closely paralleled the progress of myeli nation. Double-label in situ hybridization studies demonstrated that v zg-1-expressing cells co-expressed mRNA encoding proteolipid protein ( PLP), a mature oligodendrocyte marker, but not glial fibrillary acidic protein (GFAP), an astrocyte marker. Consistent with this, vzg-1 mRNA expression was reduced by 40% in the brains of jimpy mice, which exhi bit aberrant oligodendrocyte differentiation and cell death. Together with our characterization of vzg-1 during cortical neurogenesis, these data suggest distinct pre- and postnatal roles for LPA in the develop ment of neurons and oligodendrocytes and implicate lysophospholipid si gnaling as a potential regulator of myelination. J. Comp. Neurol. 398: 587-598, 1998. (C) 1998 Wiley-Liss, Inc.