Neural tube closure

Robinson JF et al (2010) Methylmercury induced toxicogenomic response in C57 and SWV mouse embryos undergoing neural tube closure. Reprod Toxicol 30 284-291. doi S0890-6238(10)00103-6(pii)10.1016/j. reprotox.2010.05.009... 

Earlier work by Ruddick and Khera (1975) examined this fungicide degradation product during several periods of organogenesis at doses of 10 to 80 mg/kg/day. Above 10 mg/kg they found neural tube closure defects, as well as hydrocephalus and other malformations of the brain also tail and limb deformities. Decreased brain weight was found in rabbits exposed to 80 mg/kg (ref. 183c). 

Most of the developmental toxicity evaluations of DEHP are traditionally designed studies in which physical development was evaluated just prior to birth in pups of rodents that were orally exposed during gestation only. These studies clearly show that gestational exposure to DEHP was embryotoxic and teratogenic in rats and mice. A range of effects were observed including intrauterine deaths, skeletal and cardiovascular malformations, neural tube closure defects, increased perinatal mortality, and developmental delays. 

Saitsu, H., Ishibashi, M., Nakano, H., and Shiota, K. (2003). Spatial and temporal expression of folate-binding protein 1 (Folbpl) is closely associated with anterior neural tube closure in mice. Dev. Dyn. 226(1), 112-117. 

The mechanisms by which VPA disrupts neural tube development remain largely unknown. Neural tube closure during organogenesis requires continuous cell proliferation of the neuroepithelia, and in vitro studies indicate that VPA causes cell cycle arrest in neuronal cells. These findings suggest that VPA either directly disturbs the proliferative ability of neuronal cells or perhaps alters their sensitivity to neurotrophic growth factors. 

Moephuli, S., Klein, N., Baldwin, M., and Krider, H. M. (1997). Effects of methionine on the cytoplasmic distribution of actin and tubulin during neural tube closure in rat embryos. Proc. Natl Acad. Set U.S.A. 94, 543-548. 

Although the term anencephalic suggests a lack of all but the bones of the face, in fact, all of the bones of the skull are present (Figure 6). The anomalies of the facial bones and those of the remainder of the skull are the consequence of early disruption of the notochord, the mesoderm, and the neuroepithelium. Early deficiency in neural tube closure exposes the developing brain (neuroepithelium) to mechanical abrasion from the fourth week of gestation until birth. The hindbrain (often enclosed and therefore protected by the rudimentary neurocranium) can remain intact - containing those structures responsible for control of respiration. Thus, the newborn... 

Folates are transported from the extracellular milieu to the inside of cells by either receptor-mediated (FRa) or carrier-mediated uptake (RFC). Because folates are essential for proper cellular function and necessary for neural tube closure, it is easy to envision how mutations in these receptor genes could lead to reduced levels of intracellular folates and thereby NTDs. Thus, several groups have searched for... 

The earliest of these developmental abnormalities involve the brain stem. In a unique case, Rodier et al. (1996) reported the nearly complete absence of the superior olive and facial nerve nucleus, with shortening of the brain stem between facial nerve nucleus and the trapezoid body. They concluded that the initiating injury in this autistic brain occurred around the time of neural tube closure, which occurs at about 4 weeks of fetal development (O Rahilly and Muller, 1994). This timing also corresponds to an increased incidence of autism following exposure to the drug thalidomide during pregnancy (Rodier and Hyman, 1998 Miller et al., 2005). 

Neural tube closure (neurulation) begins at stage 8 at the level of the midbrain and extends both anteriorly and posteriorly. Closixre at the rostral extremity (anterior neuropore) is complete by stage 10, whereas the posterior neuropore remains open until the tail bud develops. Soon after closure, neural crest emerges from the midbrain and hindbrain (HH stages 10-12 36 h) and, later, from the spinal cord. 

The most lateral cells of the neural plate do not participate in neural tube closure and are not recruited into the neural tube. These are the future neural crest cells, which in the truck go on to form pigment cells and neural derivatives, such as the dorsal root ganglion, and in the head form a wide variety of structures, such as the cephalic ganglia, the mandibular, hyoid, and branchial arches, and the head mesenchyme. 

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