Neural tube development
Formation of neural tube occurs by two methods:
Primary neurulation: Cells around the neural tube are directed towards the neural tube where they go through proliferation, invagination, and are pinched off from the surface to form a hollow tube.
Secondary neurulation: The neural tube comes out from the solid cord of cells. It then enters the embryo later and comes out from the hollow cavity to form the hollow tube.
Neural tube closure
The neural folds that are paired are brought together at the dorsal midline of the developing embryo or foetus. The folds attach to each other and the cells from both sides bind together. The Neural crest cells of the cranial region migrate as the neural cells fold, elevate and close. The spinal cord formation occurs after the closure.
As the neural tube length increases, the change in shape is observed. In the cephalic region (head region), the formation of the brain progresses creating swelling and constriction at various parts of brain and at the end (the tail) it tapers off. The neural tube has two open ends which are named anterior and posterior neuropores. The neural tube closure is initiated from anterior to posterior axis, but sometimes there is failure of closure at some parts of the neural tube and that results in neural tube defects.
Neural tube defects leads to the following conditions:
The human posterior part of the neural tube fails to close at the 27th day of gestation. The severity of the disease depends on the amount of exposure. If the child survives there are chances of nerve damage that may lead to neural deficits.
If the anterior part of the neural tube fails to close it results in the development of lethal condition called anencephaly. If the forebrain is exposed to the amniotic fluid, the chances of degeneration can occur. Babies with this condition die shortly after birth or are born as a stillbirth.
The failure of the whole neural tube to close at the entire axis is called cranioranchischisis.
How it occurs?
Neural tube defects (NTD’s) occur during the first month of pregnancy. The neural tube defect is present in 1.3 to 2.0 infants in 1000 live births; and it is the 2nd most common anomaly present. The environment and genetic mutations can cause NTD’s. Genetic alterations are seen where the reduced amount of folic acid and vitamin B12 is found. Vitamin B12 helps and improves the DNA metabolism as it is required to synthesize dTMP from dUMP which is responsible for the process of methylation.
Why this happens?
Although many studies have been performed no complete cause has been found yet. However, some clinical procedures show promise in its reduction.
Folate has been seen as a protective source against the development of NTD’s, specifically, for anencephaly and spina bifida. A deficiency of folic acid has been noted and has been seen to play a great role in decreasing the number of NTD’s. But sill it not enough to prevent all defects.
Another reason stated is that folic acid may not be able to act on the neural tube which can lead to a defect especially if a pregnant lady is taking anti-epileptic drugs. These drugs are contraindicated with the folic acid supplement.
Obesity is viewed as a leading cause of neural tube defect. An experiment was carried out in which it was concluded that the risk associated with maternal obesity was greater for spina bifida than for other NTD’s such as anencephaly.
Diabetes mellitus in mothers increases the chance of congenital malformation especially the neural tube defect. In a study, it was proposed that NTD’s are associated with reduced expression of the gene Pax-3, that encodes for transcription factor which carries out neural tube development, and if the expression of Pax-3 is reduced it can lead to neuroepithelial apoptosis (self-destruction of cells).
Currently, most cases of neural tube defect can be prevented with a proper diet of folic acid during pregnancy. The issues of obesity and diabetes also need proper care if present in the pregnant mother.
Dr. James Mills from the National Institute of Child Health & Development talks answers some very excellent questions about this condition. I really encourage you to watch this.
- Formation of the Neural Tube [Internet]. 2000 [cited 2013 Aug 15]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK10080/
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- Fine EL, Horal M, Chang TI, Fortin G, Loeken MR. Evidence that elevated glucose causes altered gene expression, apoptosis, and neural tube defects in a mouse model of diabetic pregnancy. Diabetes 1999;48(12):2454-62.
- Alfarra HY, Alfarra SR, Sadiq MF. Neural tube defects between folate metabolism and genetics. Indian J Hum Genet 2011; 17(3): 126-31.
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