SPINA-BIFIDA OCCULTA IN HOMOZYGOUS PATCH MOUSE EMBRYOS

In normal embryos, mRNA encoding platelet-derived growth factor A (PDG F A) and the platelet-derived growth factor receptor alpha (PDGFR alph a) are found within and adjacent to the site of vertebral development, the sclerotome, These patterns of expression are consistent with PDGF action on the developing sclerotome and dermis, Homozygous Patch (Ph) mutant mouse embryos lack the receptor gene (Pdgfra) due to an extens ive deletion at that locus, Consistent with the spatial pattern of Pdg fra expression, striking deformities are found in the spine and ribcag e of Ph/Ph embryos. In particular, we show that late-gestation Ph/Ph e mbryos have occult spina bifida involving the entire spinal column, We have analyzed the progression of the axial defects in homozygous Patc h embryos in detail, By late gestation it appears that the components of the vertebrae are present, yet the neural arches of the spine are m isshapen, We propose that PDGF A is required for proper positioning of the neural arch condensation at all axial levels, Furthermore, since the neural tube appears to close normally, we suggest that spina bifid a in the Ph homozygote is caused primarily by a semitic mesoderm abnor mality rather than a neural tube defect. (C) 1997 Wiley-Liss, Inc.