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Developmental precursor to the central nervous system

In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, and ultimately the folds meet and coalesce in the middle line and convert the groove into the closed neural tube. In humans, neural tube closure usually occurs by the fourth week of pregnancy (the 28th day after conception).

Four neural tube subdivisions each eventually develop into distinct regions of the central nervous system by the division of neuroepithelial cells: the forebrain (prosencephalon), the midbrain (mesencephalon), the hindbrain (rhombencephalon) and the spinal cord. The prosencephalon further goes on to develop into the telencephalon (cerebrum) and the diencephalon (the optic vesicles and hypothalamus). The mesencephalon stays as the midbrain. The rhombencephalon develops into the metencephalon (the pons and cerebellum) and the myelencephalon (the medulla oblongata). For a short time, the neural tube is open both cranially and caudally. These openings, called neuropores, close during the fourth week in humans. Improper closure of the neuropores can result in neural tube defects such as anencephaly or spina bifida. The dorsal part of the neural tube contains the alar plate, which is associated primarily with sensation. The ventral part of the neural tube contains the basal plate, which is primarily associated with motor (i. e., muscle) control. The spinal cord develops from the posterior neural tube. As the spinal cord develops, the cells making up the wall of the neural tube proliferate and differentiate into the neurons and glia of the spinal cord. The dorsal tissues will be associated with sensory functions, and the ventral tissues will be associated with motor functions.

The neural tube patterns along the dorsal ventral axis to establish defined compartments of neural progenitor cells that lead to distinct classes of neurons. According to the French flag model of morphogenesis, this patterning occurs early in development and results from the activity of several secreted signaling molecules. Sonic hedgehog (Shh) is a key player in patterning the ventral axis, while bone morphogenic proteins (BMPs) and Wnt family members play an important role in patterning the dorsal axis. Other factors shown to provide positional information to the neural progenitor cells include fibroblast growth factors (FGFs) and retinoic acid. Retinoic acid is required ventrally along with Shh to induce Pax6 and Olig2 during differentiation of motor neurons. Three main ventral cell types are established during early neural tube development: the floor plate cells, which form at the ventral midline during the neural fold stage; as well as the more dorsally located motor neurons and interneurons. Shh acts as a morphogen, meaning that it acts in a concentration dependent manner to specify cell types as it moves further from its source. The following is a proposed mechanism for how Shh patterns the ventral neural tube: A gradient of Shh that controls the expression of a group of homeodomain (HD) and basic Helix Loop Helix (bHLH) transcription factors is created. These transcription factors are grouped into two protein classes based on how Shh affects them. Class I is inhibited by Shh, whereas Class II is activated by Shh. These two classes of proteins then cross regulate each other to create more defined boundaries of expression. The different combinations of expression of these transcription factors along the dorsal ventral axis of the neural tube are responsible for creating the identity of the neuronal progenitor cells. Studies have shown that neural progenitors can evoke different responses based on the length of exposure to Shh, with a longer exposure time resulting in more ventral cell types. At the dorsal end of the neural tube, BMPs are responsible for neuronal patterning. BMP is initially secreted from the overlying ectoderm. A secondary signaling center is then established in the roof plate, the dorsal most structure of the neural tube. This was shown using zebrafish mutants that had varying amounts of BMP signaling activity. Researchers observed changes in dorsal ventral patterning, for example, zebrafish deficient in certain BMPs showed a loss of dorsal sensory neurons and an expansion of interneurons.