Neurulation
Neurulation is a part of organogenesis in vertebrate embryos. Steps of neurulation include the formation of the dorsal nerve cord, and the eventual formation of the central nervous system. The process begins when the notochord induces the formation of the CNS (central nervous system) by signaling the ectoderm germ layer above it to form the neural plate. The neural plate folds in upon itself to form the neural tube, which will later differentiates into the spinal cord and the brain, eventually forming the central nervous system.
Contents |
Neural plate and tube
The neural plate is a thick and flat bundle of ectoderm formed after induction by the notochord. The neural plate will develop into the neural tube which gives rise the CNS, comprised by the spinal cord and the brain.
Development
Different portions of the neural tube form by two different processes, called primary and secondary neurulation, in different species. In primary neurulation, the neural plate creases inward until the edges come in contact and fuse. In secondary neurulation, the tube forms by hollowing out of the interior of a solid precursor.
The cells of the neural plate are signaled to become high-columnar and can be identified through microscopy as different from the surrounding epiblastic ectoderm. The cells move laterally and away from the central axis and change into a truncated pyramid shape. This pyramid shape is achieved through tubulin and actin in the apical portion of the cell which constricts as they move. The variation in cell shapes is partially determined by the location of the nucleus within the cell, causing bulging in areas of the cells forcing the height and shape of the cell to change.
The process of the flat neural plate folding into the cylindrical neural tube is termed primary neurulation. The notochord plays an integral role in the development of the neural tube. Prior to neurlation, during the migration of epiblastic endoderm cells towards the hypoblastic endoderm, the notochordral process opens into an arch termed the notochordal plate and attaches overlying neuroepithelium of the neural plate. The notochordal plate then serves as an anchor for the neural plate and pushes the two edges of the plate upwards while keeping the middle section anchored. Some of the notochodral cells become incorporated into the center section neural plate to later form the floor plate of the neural tube. The notochord plate seperates and forms the solid notochord.
The folding of the neural tube to form an actual tube does not occur all at once and . Instead, it begins approximately at the level of the fourth somite. The lateral edges of the neural plate touch in the midline and join together. This continues both cranial (toward the head) and caudally (toward the tail). The openings that are formed at the cranial and caudal regions are termed the cranial and cadual neurophores. The cranial neurophore closes approximately on day 25 and the caudal neurophore on day 27. In actuality, the folding of the neural tube is still not entirely understood and is still being studied. The simplistic model of the closure occuring in one step cranially and caudally does not explain the high frequency of neural tube defects. Proposed theories include closure of the neural tube occurs in regions, rather than entirely linearly.
Primary neurulation occurs in response to soluble growth factors secreted by the notochord. Ectodermal cells are induced to form neuroectoderm from a variety of signals. Ectoderm sends and receives signals of BMP4 (bone morphogenic protein) and cells which receive BMP4 signal develop into ectoderm. The inhibitory signals chordin, noggin and follistatin are needed to form neural plate. These inhibitory signals are created and emitted by the notochord. Cells which do not receive BMP4 signaling due to the effects of the inhibitory signals will develop into the anterior neuroectoderm cells of the neural plate. Cells which receive FGF (fibroblast growth factor) in addition to the inhibitory signals form posterior neural plate cells.
After SHH from the notocord induces its formation, the floor plate of the incipient neural tube also secretes SHH. After closure, the neural tube forms a basal plate and an alar plate in response to the combined effects of Shh and factors including BMP4 secreted by the roof plate. The basal plate forms most of the ventral portion of the nervous system, including the motor portion of the spinal cord and brain stem; the alar plate forms the dorsal portions, devoted mostly to sensory processing.
Non-neural ectoderm tissue
Mesoderm surrounding the notochord at the sides will develop into the somites (future muscles, bones, and contributes to the formation of limbs of the vertebrate).
Neural Crest Cells
Masses of tissue called the neural crest that are located at the very edges of the lateral plates of the folding neural tube separate from the neural tube and migrate to become a variety of different but important cells.
Neural crest cell destinations and structures.
- Proximal to the spinal cord and line up symmetrically to form the dorsal root ganglia.
- Near the vertebral column and become sympathetic chain ganglia.
- Anterior of the aorta to become the four pre-aortic ganglia (celiac ganglion, superior and inferior mesenteric ganglia and aortical renal ganglia)
- Walls of the viscera to become enteric ganglia.
- Chromaffin cells of the adrenal medulla.
- Sensory ganglia of the fifth, seventh, ninth and tenth cranial nerves.
- Facial mesenchyme of the pharyngeal arches.
- Dentin-forming portions of teeth.
- Into the skin to form melanocytes.
- Into the developing heart and form the spiral septum.
Neural tube defects in humans
Normally the closure of the neural tube occurs around the 30th day after fertilization. However, if something interferes and the tube fails to close properly, a neural tube defect will occur. Among the most common tube defects are anencephaly, encephalocele, and spina bifida. The incidence of neural tube defects is 2.6 in 1,000 worldwide.
Pregnant women taking medication for epilepsy have a higher chance of having a child with a neural tube defect. Research has shown that women with folic acid deficiences also have a higher chance of having a child with a neural tube defect, but this is only one factor. Taking folic acid does not completely negate the risk of neural tube problems, but it does significantly reduces the risk.
References
- Thomas Sadler. (2003). Langman's Medical Embryology. New York:Lippincott Williams & Wilkins.
