Neural tube malformations such as spina bifida and anencephaly occur in 1 in 1000 births and account for 1 percent of all deaths occurring in infants under one year of age. Despite these figures, which rank these abnormalities as one of the most frequently occurring, little is known about their etiology. The purpose of this study will be to examine factors considered essential for normal neural tube development, i.e. production and maintenance of extracellular matrix (ECM) by neural fold mesenchyme and development of cytoskeletal components in neuroepithelial cells, which may also be involved in abnormal morphogenesis leading to neural tube defects. Neural tube closure in mouse embryos will be used as a model system to investigate each of these parameters and the in vitro technique of whole embryo culture will be employed to permit specific manipulation of these processes and assessments of developmental stages. The importance of ECM in neural fold mesenchyme at different stages of neural tube closure will be monitored by inhibiting its production (using diazo-oxo-norleucine) or by causing its removal (enzymatic digestion) at critical development stages during neurulation and evaluating the resulting effects on neural tube development. Characterization of the cytoskeletal structure will be undertaken by indirect immunofluorescent antibody and S-1 techniques for demonstrating the presence and localization of actin in neuroepithelial cells. Actin will be localized in fusing and non-fusing regions of neural fold development in the same embryo and in embryos of different developmental stages. Types of actin will also be determined using antibodies specific for the various forms of striated muscle and non-striated muscle actin. The role of microfilaments during neural tube closure will be determined using cytochalasins to disrupt filaments and monitoring altered patterns of actin distribution using antibody techniques. Analysis of these processes will provide valuable information concerning their role in normal and abnormal neural tube development and may suggest ways of proventing their occurrence.
| Sadler, T W; Burridge, K; Yonker, J (1986) A potential role for spectrin during neurulation. J Embryol Exp Morphol 94:73-82 |
| Sadler, T W; Horton Jr, W E; Hunter, E S (1985) Mammalian embryos in culture: a new approach to investigating normal and abnormal developmental mechanisms. Prog Clin Biol Res 171:227-40 |
| Horton Jr, W E; Sadler, T W (1985) Mitochondrial alterations in embryos exposed to B-hydroxybutyrate in whole embryo culture. Anat Rec 213:94-101 |
| Horton Jr, W E; Sadler, T W; Hunter 3rd, E S (1985) Effects of hyperketonemia on mouse embryonic and fetal glucose metabolism in vitro. Teratology 31:227-33 |
