RELATIONSHIP BETWEEN ALTERED AXIAL CURVATURE AND NEURAL-TUBE CLOSURE IN NORMAL AND MUTANT (CURLY TAIL) MOUSE EMBRYOS

Neural tube defects, including spina bifida, develop in the curly mil mutant mouse as a result of delayed closure of the posterior neuropore at 10.5 days of gestation. Affected embryos are characterized by incr eased ventral curvature of the caudal region. To determine whether clo sure of the neuropore could be affected by this angle of curvature, we experimentally enhanced the curvature of non-mutant embryos. The amni on was opened in 9.5 day embryos; after 20 h of culture, a proportion of the embryos exhibited a tightly wrapped amnion with enhanced curvat ure of the caudal region compared with the control embryos in which th e opened amnion remained inflated. Enhanced curvature correlated with a higher frequency of embryos with an open posterior neuropore, irresp ective of developmental stage within the range, 27-32 somites. Thus, w ithin this somite range, caudal curvature is a more accurate determina nt for normal spinal neurulation than the exact somite stage. Enhanced ventral curvature of the curly tail embryo correlates with an abnorma l growth difference be tween the neuroepithelium and ventral structure s (the notochord and hindgut). We experimentally corrected this imbala nce by culturing under conditions of mild hyper thermia and subsequent ly determined whether the angle of curvature would also be corrected. The mean angle of curvature and length of the posterior neuropore were both reduced in embryos cultured at 40.5 degrees C by comparison with control embryos cultured at 38 degrees C. We conclude that the sequen ce of morphogenetic events leading to spinal neural tube defects in cu rly tail embryos involves an imbalance of growth rates, which leads to enhanced ventral curvature that, in turn, leads to delayed closure of the posterior neuropore.