NORMAL DEVELOPMENT OF THE CNS

Before we review the various abnormalities that can affect the CNS, a brief overview of the normal development of the CNS is appropriate.

• Induction—After development of the three cell layers of the early embryo (ectoderm, mesoderm, and endoderm), the underlying mesoderm (the “inducer”) sends signals to a region of the ectoderm (the “induced tissue”), instructing it to develop into neural tissue.

• Neural tube formation—The neural ectoderm folds to form a tube, which runs for most of the length of the embryo.

• Regionalisation and specification—Specification of different regions and individual cells within the neural tube occurs in both the rostral/caudal and dorsal/ventral axis. The three basic regions of the CNS (forebrain, midbrain, and hindbrain) develop at the rostral end of the tube, with the spinal cord more caudally. Within the developing spinal cord specification of the different populations of neural precursors (neural crest, sensory neurones, interneurones, glial cells, and motor neurones) is observed in progressively more ventral locations. This process results from the interaction between genes whose expression defines individual territories or cell types, and diffusible signalling molecules (such as sonic hedgehog) secreted by adjacent areas of the embryo.

• Proliferation and migration—The most dorsal cells of the tube (the neural crest) migrate away to form much of the peripheral nervous system. Cell proliferation within the tube leads to thickening of the wall and many different cell types move to their correct locations. The development of the …