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18 Stem Cells and Neurogenesis

Mitradas M. Panicker, Mahendra Rao


Neural differentiation is an early embryonic event that occurs soon after germ layer specification. The newly formed ectoderm undergoes further patterning to separate into two identifiable components, the presumptive neural ectoderm and the presumptive epidermis. Neural tissue segregates as a clearly demarcated epithelium termed the neuroepithelium (or neuroectoderm). The neuroepithelium generates the central nervous system (CNS) whereas cells at the margins of the neuroepithelium will generate the peripheral nervous system (PNS). Two groups of cells contribute to the PNS. Neural crest stem cells differentiate at the neuroectodermal/epithelial junction, and placodal precursors differentiate from cranial ectoderm that lies more laterally than the zone that generates neural crest (Fig. 1). Precursors that generate the PNS also contribute to nonneural structures, including pigment cells of the skin and craniofacial mesenchyme (for review, see Le Douarin and Kalchem 1999).

Undifferentiated neural precursor cells, whether in the CNS, neural crest, or the placodes, proliferate, differentiate, and migrate to appropriate locations. Cells undergo further maturation and become postmitotic. Neuronal cells go on to project to appropriate targets, make synapses, and acquire the correct rostrocaudal and dorsoventral identity. Seminal work by a number of laboratories has led to rapid advances in our understanding of phenotypic specification (for review, see Rao 1999). An accumulating body of evidence suggests that neurogenesis follows a pattern of development similar to developmental patterns described in the liver, skin, and the hematopoietic system (Edlund and Jessell 1999; Rao 1999; Weissman 2000). In each of these systems, tissue-specific stem cells...

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