Human organoid gives insight into neural tube development

Scientists have developed a way to study processes that are crucial to the formation of the human spinal cord, without the ethical concerns of using human embryos.

Researchers from the University of California and the Gladstone Institutes, San Francisco, California, developed a model using organoids, which are clusters of cells grown in a lab to resemble mini organs. These organoids allowed them to recreate several aspects of spinal cord development, including the neural tube. This will allow scientists to investigate developmental processes that result in congenital diseases such as spina bifida.

'This is such a critical point in the early development of any organism, so having a new model to observe it and study it in the lab is very exciting,' said Dr Todd McDevitt, from Gladstone Institutes, who was senior author of the study.

In previous work, the process of neural tube development, which is the precursor for the formation of the spinal cord, could not be studied directly in humans, because it occurs after the embryo has implanted in the uterus. Therefore, studying it in vivo would be unethical.

'We can use this organoid to get at unresolved human developmental questions in a way that doesn't involve human embryos,' said Dr Ashley Libby, a postdoctoral fellow at the University of California, San Francisco, who was the study's first author.

In the study, published in Development, researchers developed a method, using signalling molecules, that enabled clusters of stem cells to undergo 'axial elongation'. This is the process where cells for the backbone and spinal cord begin to assemble and form distinct 'head' and 'tail' regions. The results were exciting because axial elongation is not usually seen in organoid models.

Once they developed their model, the scientists used the genome editing approach CRISPR/Cas9 to silence certain genes and work out which ones are crucial for axial elongation and neural tube development.

In the future, these organoid models could be used to study the effects of different factors on embryo development and investigate whether they lead to birth defects. Dr Libby explained, 'for instance, you could add chemicals or toxins that a pregnant woman might be exposed to and see how they affect the development of the spinal cord.'