neural tube defects

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The embryonic neural tube gives rise to the central nervous system - the brain and spinal cord. Therefore, any problems which arise during development of the neural tube can have serious consequences. There are many different neural tube defects. Anencephalus is where significant parts of the brain, particularly the cerebral hemispheres, fail to develop correctly, and spina bifida involves a region of the spinal cord. We will consider some embryological aspects of spina bifida.

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spina bifida

At first sight, there appear to be two possible ways in which a localised spina bifida lesion could arise:

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the neural plate could fail to fold and close correctly

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or the neural tube might form correctly and then burst open for some reason

two hypotheses: non-closure or secondary opening

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The following images are cross-sections through the neural plates of early chick embryos in regions where development is progressing towards spina bifida. They show different degrees of non-closure of the neural tube and the responses of nearby tissues:

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In this cross-section closer to the tail region of the embryo, the neural tube is closed but has a septum separating two central lumina rather than having a single central lumen:

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Although most of the neural tube is formed by folding and closure of the neural plate, the most caudal (tail-ward)part is added on by a different process. Cells are built on to the caudal end of the already formed part of the tube in a region called the tail bud. In the following image, a collage of photos on the left shows the full length of a living chick embryo, while a labelled diagram on the right shows the location of the tail bud:

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Here is a photo of the tail bud of a living chick embryo:

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The transitional region between primary neurulation, where the neural tube is being formed by the neural plate, and secondary neurulation, where the last part of the neural tube is being formed by the tail bud, is a place where things can sometimes go wrong resulting in spina bifida. It is located in the future lumbosacral region of the embryo, and this is a site where spina bifida most commonly occurs in human babies.

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The different patterns of neural tissue that we saw in the cross-sections through embryos with spina bifida are the result of the different processes contributing to the formation of the neural tube - primary and secondary neurulation. This diagram relates the different profiles to different regions of the neural tube:

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When a spina bifida lesion develops in the transitional region between primary and secondary neurulation, it has several characteristic features. The lesion has a complex morphology, and there will be a succession of knock-on effects on the development of surrounding structures. The diagram below summarises some of the main embryological features:

Embryological features of a spina bifida lesion

1. continuity between the neural tissue and adjacent ectoderm is lost
2. an ectodermal spur grows ventrally alongside the neural tissue
3. there is increased cell death in the exposed neural tissue
4. a separate lumen is developing within the tail bud contribution
5. the luminal surface of the unclosed region of the neural plate is exposed
6. at the cranial end of the lesion the neural folds are forming a midline septum
7. neural crest cells are forming an irregular mass where neural closure began to fail
8. enlarged blood vessels are forming alongside the lesion and penetrating the neural tissue
9. the somites are less regular in this region

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So, returning to the working hypotheses at the beginning regarding the possible origin of spina bifida - either non-closure or secondary opening - we can see that in reality the picture is more subtle and complicated. In the transitional region, the caudal neuropore may fail to close properly, and the contribution of the tail bud cells becomes compromised. The result is a morphologically complex lesion in which the different cell types are trying to make the best of an abnormal arrangement at that stage of development.

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