Normal and abnormal neurulation in humans: Implications for the pathogenesis of neural tube defects

Abstract

The closure of the neural tube (NT) in humans has generally been described as a continuous process that begins in the region of the future neck and proceeds both rostrally and caudally, Recently, four separate initiation sites for neural tube fusion have been demonstrated in mice and other experimental animals. In humans, based on the study of neural tube defects (NTD) in clinical cases, van Allen et al. proposed a multisite NT closure model which argued that five closure sites exist in the NT of human embryos.1 By direct observation of human embryos with the fusing NT (Congenital Anomaly Research Center, Kyoto University, Kyoto, Japan), it was revealed that NT closure in human embryos does initiate at multiple sites but that the mode of NT closure in humans may be different from that in rodent species. In addition to the future cervical region which is widely accepted as an initiation site of NT closure, the mesencephalic‐rhombencephalic border was found to be another initiation site. Because there may be such species difference in the mode of NT closure, we should be careful when extrapolating data from experimental animals as it may not apply to humans. It is likely that the type of NTD affects the intra‐uterine survival rate of human embryos with NTD. Almost all of the embryos with total dysraphism appear to die by 5 weeks of gestation. while those with an opening over the rhombencephalon appear to die by 6.5 weeks, and those with a defect at the frontal and parietal regions survive beyond 7 weeks.