During normal embryonic development, several tissues must come together to form the spine and nervous system. In a typical pregnancy, neurulation (the formation and closure of the neural tube) occurs very early – around the third to fourth week after conception, often before a woman even knows she’s pregnant (Cleveland Clinic, 2022). The neural tube is a structure made of tissue that will later develop into the central nervous system (the brain and spinal cord). At the same time, the tissues around it form the protective structures: the bones of the spine (vertebrae), the meninges (protective membranes around the spinal cord), and the skin that covers the back. Normally, the neural tube closes completely along the back, and the vertebrae then close around it, forming a continuous spinal column encasing the spinal cord (Cleveland Clinic, 2022). The top of the neural tube closes to form the brain, and the bottom (caudal) end of the tube closes to form the lower spinal cord. When this process proceeds correctly, the result is an intact spine and nervous system.

In spina bifida, there is a failure of proper tissue development during those early weeks, specifically a failure of the neural tube to close fully in the lower (caudal) region. Because the neural tube doesn’t close, the developing vertebrae (spinal bones) cannot form a complete ring around the spinal cord. Essentially, one or more vertebrae are “split” or missing their back portion (the spinous process and laminae), leaving a gap in the spine. The overlying skin may also be absent or incompletely formed in that area. As a result, the delicate spinal cord and nerves may protrude out through the gap, or be covered only by a thin membrane. This open spine defect is what defines spina bifida (CDC, 2024b). The degree to which the spinal tissues protrude or remain enclosed differentiates the types of spina bifida.

Spina Bifida Occulta

In this form of spina bifida, the tissue involvement is minimal. Only the bony vertebrae are affected, typically with one vertebra (often in the lower back) not fully closing. The spinal cord itself develops normally and remains in place. The meninges are not exposed, staying inside the spinal canal. The skin over the defect is intact, and so there is generally no nerve damage in occulta, and as mentioned, it usually causes no neurological symptoms (CDC, 2024b). Many people with occulta never know they have it. Occasionally, tethering of the spinal cord can occur (where the cord is abnormally attached, limiting its movement within the spinal column), but this is more often a concern in other variants like lipomeningocele rather than true occulta. From a tissue standpoint, occulta essentially involves only bone (and sometimes a slight abnormality in the overlying skin or fat), but nervous tissue is not disrupted.

Meningocele

Here, the defect is larger: the gap in the vertebrae allows the meninges—the membranes that surround the spinal cord—to balloon outwards, forming a sac filled with cerebrospinal fluid. Think of it as a protruding cyst covered by a thin layer of skin (or sometimes by a membrane if skin is partly absent). Importantly, in meningocele the spinal cord itself remains inside the spinal canal; it does not herniate into the sac (CDC, 2024b). This means nervous tissue is generally intact and where it should be, though it may be displaced slightly by the fluid sac. Because the nerves are not exposed or as damaged, meningocele often results in milder disabilities. Many babies with meningocele, once the sac is surgically removed and the opening closed, have little or no neurological impact, though some may have minor issues. The main tissue involved here is the meningeal membrane (and fluid) bulging out; the bones failed to fuse; the skin may be thin over the sac.

Myelomeningocele

In the most severe cases of spina bifida, multiple tissues are involved. There is a significant opening in the spine, and through this opening both the meninges and the spinal cord tissue protrude. The term “myelo” refers to spinal cord, indicating the spinal cord is part of the exposed sac (CDC, 2024b). In these cases, the spinal cord is often dysplastic (abnormally formed) and damaged from the in utero exposure to amniotic fluid and mechanical trauma. There may be little to no functional neural tissue across the defect. The exposed nerves in the sac are extremely vulnerable. The skin is usually absent over the area, meaning the sac is covered only by a thin membrane, or sometimes it’s open leaking spinal fluid at birth. This means that at the tissue level, myelomeningocele is a complex lesion: it involves malformed bone (open vertebrae), missing skin covering, herniated meninges, and herniated/damaged neural tissue (spinal cord and nerve roots). This is why myelomeningocele causes moderate to severe disabilities, such as paralysis of the legs and loss of sensation below the lesion (CDC, 2024b; UCSF Benioff Children's Hospitals, n.d.). The higher on the spine the lesion occurs, the more of the body is affected. For example, a myelomeningocele in the upper back (thoracic region) will affect everything below that point (possibly the legs and trunk), whereas one in the lower back (lumbar region) might only affect the legs and pelvic organs. Besides paralysis and orthopedic issues, the exposed spinal tissue in myelomeningocele disrupts the normal flow of cerebrospinal fluid. Nearly all infants with myelomeningocele develop hydrocephalus because the hindbrain (cerebellum) is pulled downward—a condition known as the Chiari II malformation – blocking fluid circulation (UCSF Benioff Children's Hospitals, n.d.). This requires surgical management (shunting) in many cases.

Big Picture

The differences in these tissue-level outcomes explain the differences described in Symptoms. In summary: when only bone is involved (occulta), there are often no symptoms. When the meninges protrude but not nerves (meningocele), symptoms are either very mild or related to the presence of the sac (which can be corrected with surgery). When the spinal cord tissue itself is involved (myelomeningocele), the nerve damage leads to significant, lifelong impairments like paralysis and organ dysfunction.

Spina bifida primarily involves tissues of the central nervous system (spinal cord) and its protective coverings. However, it can have secondary effects on other body systems. For instance, because the lower spinal cord controls bladder and bowel function, many individuals with myelomeningocele have urogenital and gastrointestinal involvement – neurogenic bladder (requiring catheterization to empty) and neurogenic bowel (requiring bowel programs to manage). The musculoskeletal system is affected due to muscle paralysis or imbalance – leading to clubbed feet, hip dysplasia, or spinal curvatures. The skin can be affected by poor sensation (leading to pressure sores if one uses a wheelchair or braces). Even the brain structure can be impacted (in Chiari II malformation, part of the brainstem is displaced).

To understand spina bifida better before thinking of treatment options, scientists often turn to model organisms. The process of neural tube closure is a fundamental biological event that can be studied in animals. Mouse models in particular have been invaluable. There are strains of laboratory mice that naturally develop neural tube defects very similar to spina bifida. For example, the “curly tail” mouse has a genetic mutation that causes a portion of the neural tube to close late or incompletely, resulting in spina bifida in some offspring. This model has been used for over 50 years to study how genetics and maternal diet affect NTDs (Sudiwala et al., 2016; van Straaten & Copp, 2001). Another famous model is the “loop-tail” mouse, which carries a mutation in a gene that is critical for a cellular signaling pathway during development (this mutation affects the Vangl2 gene, discussed in Genes and Signaling Pathways). Loop-tail mice have severe open neural tube defects and have provided insight into the molecular interactions needed for the neural tube to seal up (Fernández-Santos et al., 2023; Galea et al., 2018). Researchers also use chicken embryos and other models to observe neurulation in real-time and test interventions, since chick embryos are accessible in the egg. Through these models, scientists have learned that certain nutrients like folic acid and inositol can prevent some neural tube defects, and they’ve identified many genes that, when disrupted, lead to spina bifida-like conditions in animals. These discoveries are directly relevant to humans. In fact, the reason we know folic acid is so important is because of both human epidemiological data and animal experiments confirming its role in neural tube closure. Animal models paved the way for fetal surgery: before surgeons attempted to repair spina bifida in human fetuses, they practiced the technique in animal pregnancies (such as pregnant sheep and monkeys) to refine the procedure and demonstrate improved outcomes.

In summary, the tissues involved in spina bifida are primarily the neural tissue (spinal cord), mesenchymal tissue that forms bone (vertebrae), and the protective membranes (meninges and skin). The normal sequence of these tissues developing and closing is interrupted. This structural problem then leads to the functional problems (symptoms) we see in affected individuals. Understanding which tissues are involved and how they develop abnormally has been crucial for developing both preventive measures (like folate supplementation) and treatments (like surgical repair).