Neural Tube Defects
During the early stages of human development, the embryo goes through a stage where it becomes
multilayered. The three layers, once formed, then further develop into specific tissues in the adult. The
three tissues are…
Ectoderm (the outer layer) becomes the epidermis (top layer of the skin) and nervous system
Mesoderm (the middle layer) becomes bone and muscles
Endoderm (the inner layer) becomes the digestive system and the respiratory system
For this lecture material, we are primarily interested in the ectoderm and the decision to become either
epidermis or nervous system. The notochord (a key structure in our own classification among similar
organisms) is a rod of tissue that lies underneath the ectoderm near the back of the embryo. It secretes
proteins that “tell” the overlying ectoderm to become neural, more specifically the neural plate. Changes
within the neural plate allow it to fold up into a tube (neural tube). This tube becomes the brain in the
anterior region of the embryo and the spinal cord in the posterior region of the embryo.
Therefore, the complete closure of the neural tube (neurulation) is an important event in the
development of the nervous system and failure to close properly is associated with neural tube defects
(NTDs). NTDs occur roughly in 1/1000 live births. This closure occurs at several points along the
anterior-posterior axis and towards the anterior (anterior neuropore) and posterior (posterior
When failure to close occurs near the head, anencephaly occurs because the forebrain is open to the
amniotic fluid and degenerates. Towards the posterior region, failure to close results in spina bifida and
total closure results in Craniorachischisis.
Causes of neural tube defects
-There are over 300 genes that normally contribute to proper neural tube closure. Therefore, it
isn’t a surprise that mutations in some of these genes lead to problems in humans and mice
-Environmental factors also influence proper neural tube closure.
Drugs, diabetes, obesity, and toxins have been shown to be causes of NTDs.
Maternal dietary factors like cholesterol and folic acid (folate) have links to this process.
We discussed 4 different pieces of evidence for how folic acid contributes to lower the rate of NTDs in
newborns. At least one hypothesis is that it contributes epigenetically to control changes in gene
expression through histone/DNA methylation.
a. Adding folic acid to certain foods lowers the rate NTDs in the overall population and in animal
b. A binding protein for folic acid (Folic acid Binding Protein) is present in the region where the
neural tube fuses together before and during closure.
c. Mutations in the gene for Folic acid Binding Protein lead to neural tube defects in mice
d. Moms who give birth to children with NTDs have been found to produce antibodies to the Folic
acid Binding Protein while moms who do not give birth to NTD children do not produce
We finished up by briefly talking about patterning and how tissues must be told where to be made in the
embryo. The neural tube must be patterned along several axes and we focused on the Dorsal-Ventral
axis. You will notice that sensory neurons (the neurons allowing us to receive sensory input from the
periphery – like our fingertips) enter the spinal cord through the back region (dorsal) of the neural tube.
On the opposite ventral side motor neurons leave the neural tube in order to stimulate muscles in the
periphery (like the muscles in our hands and arms).
Therefore, the neurons along the dorsal-ventral axis are different. They become different because the
notochord (which is closest to the ventral side of the neural tube) secretes Sonic Hedgehog protein. As