Neural tube defects induced by B-D-xyloside: evidence of a role for sulfated proteoglycans in neural fold fusion in rat embryos

Neural fold fusion in considered the final step in primary neurulation. Although a failure in neural fold fusion has been suggested to be responsible for many neural tube defects, one of the most prevalent congenital malformations in humans, to date the developmental mechanisms involved in this process remain unclear. In this paper we explore how sulfated proteoglycans might play a key role in this important process.Rat embryos whose neural folds were in close proximation were explanted and cultured in vitro for 24 hours, either with or without B-D-xyloside. Treated embryos displayed neural tube defects, normally located at the mesencephalo-rhombencephalic roof. These embryos featured subquent defects in brain development, with a generalized failure in brain vesicle expansion and abnormal infoldings of neuroepithelial walls inside the brain cavity.These results provide experimental support for the hypothesis that sulfated proteoglycans, probably associated with the extracellular matrix intercalated among meural folds, play a key role in the fusion process.