Neurulation is the formation of the neural tube from ectodermal cells during embryonic development. The neural tube later develops into the individual structures of the central nervous system. In neurulation disorders, the formation of the neural tube is defective, which can result in various malformations of the nervous system.
What is neurulation?
Neurulation, in the context of embryonic development, is the formation of the neural tube from ectodermal cells. This is an embryonic tissue structure that forms from day 19 of embryonic development. The human embryo differentiates into different cell layers at the beginning of embryonic development. These cell layers are called cotyledons and are formed during gastrulation. Humans are triploblastic and thus have three germ layers: the inner entoderm, the midline mesoderm, and the outer ectoderm. The germ layers are programmed to develop specific tissues. The development of the central nervous system in vertebrates begins with the formation of the so-called neural tube. This is an embryonic tissue structure that forms from the convergence and fusion of the neural folds beginning on day 19 of embryonic development. This process is called neurulation and corresponds to the folding of the neural ectoderm from the primary structure of the external ectoderm. Neurulation occurs under the influence of signaling substances. These messengers originate from cells of the axial mesoderm.
Function and task
Primary neurulation proceeds in phases. Initially, the neural plate demarcates at the surface of the ectoderm. The rostral ectoderm area in front of the primordial mouth and primitive streak thickens into a sole shape during these processes. In the next phase, the neural plate margins bulge to form neural bulges, giving rise to a depression in the middle called the neural groove. The cells of the middle line attach to the notochord and form the deepest point of the neural groove. During the subsequent phase, the neural ridges form neural folds. These folds meet in the middle in a wide course and close the neural groove by their fusion. Thus, the former neural groove becomes the neural tube. Neural fold fusion takes place on the basis of (N-)cadherin molecules of the cell membranes. In the next phase of neurulation, the neuroectoderm separates from the outer cotyledon. The remaining ectoderm grows together above it to form the surface ectoderm and migrates into the embryo interior. The cells of the former neural plate margin form so-called neural crests on both sides of the neural tube. The neural tube is the origin of the central nervous system. It folds off around the 25th day of development. The anterior opening of the structure closes before the posterior opening closes, allowing the brain to develop in the anterior section of the neural tube. The more posterior sections form the spinal cord. Neurulation is induced by second messengers derived from the notochord. Protein factors such as noggin and follistatin inhibit progression to surface epithelium and allow access to developmental genes for nervous tissue. Together with growth factors, they are involved in regional differentiation of structures. In the medial neural plate, the cells of the ectoderm are anchored to the notochord with selectivity. They are first located in medial lineages and later merge into two dorsolateral formations, thus forming the fulcrums for the formation process. Cell shape changes can thus be achieved via precisely coordinated rearrangements of cytoskeletal parts. In coordination with the growth processes of the cell compound, the bulging or retraction of certain structures is thus achieved. In the form of an abutment, the fixed pivot points enable such coordinated growth and thus precise shaping of the neural tube. During secondary neurulation, fluid-filled cavities form in the cell strand and coalesce into a tubular structure. The structure becomes connected to the lumen of the structure and is filled by the neuroepithelium. Thus, in the second embryonic month, a caudal segment is attached to the neural tube, which is composed of mesodermal cells and develops into the caudal segment of the spinal cord. This secondary neurulation is initiated in humans but does not continue to form an implied tail structure.
Diseases and ailments
Incomplete or defective neurulation results in malformations of the central nervous system. Neurulation disorders are also called dysraphias and are divided into different subtypes depending on the time of their onset. Detachment disorders of the neural tube form a large group of dysraphias with different manifestations. When neurulation disorders begin in the third and fourth weeks of gestation (pregnancy), dysraphic malformations of the nervous system develop. Such malformations are due to disturbances in the closure of the neural tube and can manifest themselves, for example, in a cleft formation of the skull with meningeal and cerebral defects. Craniorachischisis totalis is probably the most pronounced form of neurulation disorder and exposes the brain and spinal cord to open amniotic fluid. Connective tissue formations are present instead of neuronal tissue. Anencephaly is a somewhat milder malformation. In this disorder, the cranial dome is absent, but the brainstem and cerebellum are usually present. Children with this milder form nevertheless rarely survive the first few months. Midline defects are also neurulation disorders and are associated with brain malformations or secondary brain damage. An example of disorders of this type is Meckel-Gruber syndrome. Neurulation disorders are among the most common in the spinal cord. Spina bifida occulta is the best example of such a manifestation, which is often asymptomatic. Spina bifida cystica also affects the spinal column and is associated with paralysis and sensory disturbances. In this context, an open form is distinguished from a hyperskinned form. Other malformations based on neurulation disorders include syringomyelia and diplomyelia.
