The neuroepithelium generates the central nervous system, including the brain and spinal cord. This tissue layer emerges very early in embryonic development from the ectoderm, one of the three primary germ layers of the embryo. It represents the initial population of neural stem cells, possessing the unique capacity to both self-renew and give rise to the immense diversity of cells that make up the mature nervous system.
Defining the Neuroepithelium
The neuroepithelium initially forms the neural plate, a thickened region along the midline of the developing embryo, which then folds inward to create the neural tube. This tissue is structurally categorized as a pseudostratified columnar epithelium, meaning it appears to have multiple cell layers despite all cells resting on the same basal surface. The crowded appearance is created by the nuclei of the neuroepithelial cells residing at different heights within the single cell layer.
Each neuroepithelial cell spans the entire thickness of the neural tube wall, connecting an inner, or apical, surface with an outer, or basal, surface. The apical ends of these cells face the central fluid-filled cavity, the lumen of the neural tube, and are tightly connected by specialized structures called adherens junctions. This distinct epithelial organization and polarity are maintained throughout the early stages of nervous system formation.
Stem Cell Properties and Proliferation
The neuroepithelium acts as the primary progenitor pool for the developing nervous system, maintaining its population through cell division. During the initial phase of development, these cells undergo symmetric proliferative divisions, where one cell divides to produce two identical neuroepithelial daughter cells. This process rapidly expands the number of progenitor cells, allowing the neural tube wall to thicken dramatically.
As development progresses, the neuroepithelial cells gradually transition into radial glial cells, which are considered the neural stem cells of the developing brain. These elongated radial glia then switch to an asymmetric division mode, producing one self-renewing radial glial cell and one differentiating daughter cell. The nuclei of these cells exhibit interkinetic nuclear migration, moving up and down the length of the cell in synchronization with the phases of the cell cycle, a unique feature that coordinates division at the inner surface.
Differentiation and Formation of Neural Structures
The differentiating cells produced by the radial glia are the precursors to the neurons and glial cells found in the adult central nervous system. This transition from progenitor to mature cell type follows a specific chronological pattern known as neurogenesis, occurring before the subsequent phase called gliogenesis. Early in development, the asymmetric divisions primarily yield neurons, which migrate away from the inner ventricular surface along the long, slender processes of the radial glial cells.
The radial glial cells serve as temporary scaffolds, physically guiding the newly formed neurons to their final positions within the developing brain layers. After the main period of neuron production is complete, the radial glia change their output to focus on gliogenesis, generating the macroglia of the CNS.
This second wave produces astrocytes, which provide structural and metabolic support, and oligodendrocytes, which are responsible for creating the insulating myelin sheaths around axons. The coordinated differentiation of these cell types from the neuroepithelium and its radial glial derivatives is what forms the distinct regions of the brain and the spinal cord.
Specialized Neuroepithelial Tissues
Beyond forming the main structures of the CNS, neuroepithelium gives rise to several specialized tissues. The olfactory neuroepithelium, located in the nasal cavity, contains sensory neurons that are responsible for detecting smells. Uniquely, this neuroepithelium retains a population of stem cells that continuously replace the olfactory sensory neurons, which have a short lifespan.
Another specialized derivative is the Retinal Pigment Epithelium (RPE), a single layer of pigmented cells situated behind the photoreceptors of the eye. The RPE performs several functions that are necessary for vision: it transports nutrients to the photoreceptors, absorbs stray light, and is responsible for recycling visual pigments. The RPE also regularly phagocytizes, or consumes, the shed outer segments of photoreceptor cells.
Clinical Significance and Malformations
Disruptions in the development of the neuroepithelium can lead to severe congenital malformations. The failure of the neural plate to fold and fuse into the neural tube results in Neural Tube Defects (NTDs). Two of the most common and severe NTDs are anencephaly, where the brain fails to develop due to the opening of the cranial neural tube, and spina bifida, which involves an incomplete closure of the spinal cord.
These closure failures are often linked to issues with the neuroepithelial cells’ ability to regulate their shape and undergo apical constriction, a force-generating mechanism needed for the tissue to bend. Furthermore, the neuroepithelial cell lineage can be the source of certain brain tumors, such as Dysembryoplastic Neuroepithelial Tumors (DNT). These tumors arise from the abnormal proliferation of cells with neuroepithelial or radial glial characteristics, illustrating the potential consequences when the normal controls on stem cell division are lost.