Histological study of the cranial neural folds of mice genetically liable to exencephaly.

The SELH/Bc (SELH) inbred stock of mice has a high liability to the neural tube closure defect, exencephaly. All SELH embryos close their cranial neural tubes by an abnormal mechanism, lacking elevation and initiation of fusion in the posterior prosencephalon/anterior mesencephalon region. Most embryos complete closure of the cranial neural tube by extension of a more rostral site of fusion, but in 10-20% this process fails, and the embryos are subsequently exencephalic. In this study, transverse histological sections of the cranial neural folds of SELH embryos at the 3-5, 6-8, and 9-11 somite stages were compared to those of two strains with normal neural tube closure, ICR/Bc and LM/Bc. At all stages, consistent morphological differences were observed between SELH and the two normal strains. In 3-5 somite SELH embryos, the divergence of the folds from the neural groove is more angular, the folds are flatter, and their lateral tips appear "hooked" downward. In 6-8 somite SELH embryos, the lateral tips of the folds appear more elongated and in the prosencephalon they are less elevated than in the normal strains. The boundary between neuroepithelium and mesenchyme or surface ectoderm tends to be less clear than normal in SELH lateral tips. In 9-11 somite SELH embryos, divergence of the folds from the neural groove continues to be angular and the lateral folds are splayed horizontally. In addition, the lateral surface ectoderm is abnormally indented and the neuroepithelium/surface ectoderm boundary is more ventral and lateral in SELH than in ICR/Bc and LM/Bc. The hypothesis that the defect in SELH cranial neural folds might involve the cytoskeleton was tested using a fluorescent probe for filamentous actin in 7 somite SELH and ICR/Bc embryos. The actin staining pattern in SELH embryos was like that of normal ICR/Bc embryos, with a strongly staining apical concentration in the neuroepithelium. This suggests that there is no gross cytological abnormality within the neuroepithelium, but does not rule out more subtle defects, such as those involving cytoskeletal function.