Abstract
Human neural tube closure occurs during the third to fourth gestational week, often before people realize they are pregnant. Ethical issues limit collection of embryonic human neural tube tissue. However, the development of human neural tube organoids is beginning to empower the study of neural tube closure and neural tube defects. A previous review summarized human neural tube organoid models which are grown on top of or embedded in Matrigel or Hydrogel. Recent advances in human neural tube organoid models through micropatterned or microfluidic methods recapitulate diverse and complex neural tube features. In this review, our goal is to summarize these human iPSC-derived advanced organoid models. Moreover, these organoid models provide the possibility of testing how environmental factors influence the process of neural tube closure. Focusing on folic acid supplementation which can reduce the prevalence of neural tube defects, we review experimental evidence for three molecular mechanisms of folic acid function. Our perspective is to boost research on the impacts of environmental factors on reducing the risk of neural tube defects by utilizing human neural tube organoid models.