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Central nervous system (CNS) embryology is a broad subject. This topic summarizes CNS organogenesis and reviews the framework of embryology, the embryogenesis of the brain and spinal cord, various in-utero tests for CNS anomalies, and problems that may be encountered during embryogenesis, with particular attention to the CNS. The CNS system involves 3 germinal layers: ectoderm, mesoderm, and endoderm. The ectoderm is the primary driver of CNS development during embryogenesis. It differentiates into surface ectoderm, which forms the epidermis, hair, and nails, and neural ectoderm, which gives rise to the neural tube and neural crest. These structures subsequently develop into the brain, spinal cord, and peripheral nerves. The endoderm gives rise to the lining of the gastrointestinal and respiratory systems. It also gives rise to abdominal organs such as the liver, pancreas, and bladder. The mesoderm differentiates into 3 primary regions, each with distinct developmental contributions. The paraxial mesoderm consists primarily of somites, which develop into the axial skeleton, dermis, and skeletal muscles. The intermediate mesoderm gives rise to the gonads, kidneys, and other urogenital structures. The lateral plate mesoderm is further divided into parietal and visceral layers, with the parietal mesoderm forming the limb skeleton and the visceral mesoderm contributing to the muscular wall of the gut tube. Embryological Transformations Because these changes do not occur at once, embryology is a complicated subject. The following embryonic development timeline, with particular attention to the CNS, provides a clearer understanding of the process. Weeks 1 to 3: Zygote formation, blastocyst, and gastrulation occur. Mid-fourth week: Embryo is linear and uniform; notochord formation occurs. Late-fourth week: Many forms of differential growth occur; upper limb buds always develop before the lower limb buds. Fifth week: Limb buds are more pronounced. Sixth week: Can begin to see eyes and auricular hillocks, which develops into the external ears. Seventh week: Formation of eyes, ears, and fingers. Late eighth week: Formation of all organ systems. Nine to 12 weeks (11 to 14 gestational age): Embryo has a large head and a small body, and the body grows to catch up with the limbs. The genitalia can be recognized during this period, giving a chance for parents to find out the gender of the embryo.

Seventh week: Formation of eyes, ears, and fingers. Late eighth week: Formation of all organ systems. Nine to 12 weeks (11 to 14 gestational age): Embryo has a large head and a small body, and the body grows to catch up with the limbs. The genitalia can be recognized during this period, giving a chance for parents to find out the gender of the embryo. Thirteen to 16 weeks (15 to 18 gestational age): Coordinated limb developments and ossification of skull occur; Ovaries differentiate and contain primordial ovarian follicles that contain oogonia; the eyes face anteriorly, and ears are in place. Seventeen to 20 weeks (18 to 22 gestational ages): Eyebrows and head hair are visible at 20 weeks. Twenty-one to 25 weeks (23 to 27 gestational age): Type II pneumocytes secrete surfactant. It is after this stage that babies are considered viable. Twenty-six to 29 weeks (28 to 31 gestational age): Eyelids open; the quantity of white fat increases. The CNS has matured and can control breathing and temperature regulation. Additionally, the bone marrow takes over (from the yolk sac) as the major site of erythropoiesis. Thirty to 34 weeks (32 to 36 gestational age): Maturation and growth of organs occur. Thirty-five to 38 weeks (37 to 40 gestational age): Baby now has a firm grasp with hands. Testes may have descended in males.[1][2]

Embryogenesis can be complex and may result in mild or severe defects (pathophysiological changes). Teratogenesis is defined as any external factor that can influence the growth of the embryo. Embryos are highly susceptible and critical between weeks 3 and 8, when organ systems develop. Dysraphism is the failure of fusion between the symmetric halves of an anatomical structure. These include, and are not limited to, spina bifida malformations. Spina bifida occulta occurs when the vertebral column fails to fuse, but other layers develop normally. It is the least severe form of dysraphism and usually affects the lumbosacral region (S1 to S2 most commonly). It can be associated with moles, angiomas, lipomas, and abnormal hair growth in the affected area. Spina bifida aperta occurs when there is an incomplete fusion of the skin with or without a cyst. The spinal cord is still covered by the arachnoid mater, thus preserving the subarachnoid space and preventing leakage of the cerebrospinal fluid. Spina bifida cystica is the most severe form of dysraphism. Patients may develop urinary or fecal incontinence. 80% of these lesions occur in the lumbosacral region. Dysraphism in the cranium causes malformations analogous to spina bifida: Encephalocele: Protrusion of the brain into the subarachnoid space. It can be associated with Chiari III malformation, in which part of the cerebellum protrudes, and the spinal cord becomes twisted. This is commonly associated with cleft lip and palate. Anencephaly is characterized by the absence of the cerebral cortex and thalamic structures, with the cerebellum, brainstem, and spinal cord present (though they may be deformed). This can occur due to failure of notochord signaling, which is necessary for median hinge point formation or for the induction of neural crest cell maturation. Holoprosencephaly: Failure of features to form along the midline of the face. Features include a single central incisor, cyclopia, or an unpaired cerebral hemisphere. Craniorachischisis totalis is when the entire neural plate fails to fold, and the CNS is open to the amniotic cavity. These are often associated with stillborn fetuses.[8]