Neural tube defects: A review of human and animal studies on the etiology of neural tube defects

Abstract

Although neural tube defects are a common congenital anomaly, their etiology is not known. Human studies have emphasized the pathology and epidemiology of the defects and suggest that in the majority of cases the etiology is multifactorial. Factors which appear possibly to be important are genetic predisposition, maternal illness, and fetal drug exposure. Animal studies have utilized naturally occurring neural tube defects and teratologically induced lesions. No animal model has been convincingly established as the equivalent of human neural tube defects. However, animal models have allowed investigation of the mechanisms of suggested human teratogens and determination of the pathogenesis of naturally occurring animal defects. Their most important contribution has been in furthering the understanding of the normal mechanisms of neural tube closure. It may be through this understanding that the etiology of human neural tube defects will be determined.

Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network

“…One of the most intensely studied populations of morphogenic epithelia is that which gives rise to the adult brain and spinal chord, as defects in neural tube closure effect approximately 0.1% of human births, resulting in spina bifida and anencephaly (Campbell et al, 1986;Copp et al, 1990a). The neural tube is generated from polarized ectodermal epithelium that undergoes a series of well-defined morphogenetic movements that convert the flat neural plate into the closed neural tube (Colas and Schoenwolf, 2001).…”

Embryology of myelomeningocele and anencephaly

“…50 Although these all suggest a number of potential mechanisms whereby NTDs might arise, the cause of human malformations remains unknown. Neural tube defects are most likely heterogeneous in origin 8,10,11,17 and represent the end result of a various embryonic disorders.What is clear, however, is that NTDs represent the intricate interactions between complex genetic and environmental factors. Many lines of evidence point to a genetic component for NTDs.…”

“…17 Because early neural embryogenesis in general, and neurulation in particular involve a complex interplay of multiple cellular processes, tissue morphogenesis, and the timely expression of multiple transcription and cell signaling factors, it is not surprising that NTDs may result from a number of embryonic insults. Neural tube defects have been produced experimentally using a number of teratogens, 8 genetic mutations, 10,11,31 and experimental manipulations. 50 Although these all suggest a number of potential mechanisms whereby NTDs might arise, the cause of human malformations remains unknown.…”

Fetal Anal Incontinence Evaluated by Amniotic Fluid Digestive Enzyme Assay in Myelomeningocele Spina Bifida

“…The cause of spina bifida is unknown and probably multifactorial (1). The most generally accepted pathogenetic mechanism is a primary disorder of neurulation with failure of the embryologic neural plate to close (2).…”