Neural Crest Differentiation

The neural crest is a transient embryonic cell structure generated from the neuroectodermal plate upon closure of the neural tube (Le Douarin and Ziller 1993). Migrating neural crest cells from the trunk region of the embryo generate neuronal and glial cells of the peripheral nervous system, neuroendocrine and sensory ganglion cells, as well as non-neural pigment and smooth muscle-like cells. An important aspect of neural crest development germane to NB is that cell division continues along with the progressive restriction of differentiation potential and is even present in adrenal medullary cells postnatally (Mascorro and Yates 1989). Thus, two seemingly divergent cellular programs are operating simultaneously: proliferation and differentiation.

Excellent studies have highlighted the amazing pluripotent nature of the neural crest anlage. Detailed studies using a chick/quail chimera showed that the local tissue microenvironment plays a pivotal role in effecting the differentiation lineages (Le Douarin and

Ziller 1993). More recently, restrictive signaling factors that promote commitment to particular cell fates in migratory and postmigratory neural crest precursor cells have been delineated (Lo et al. 2002; Hemmati et al. 2003; Luo et al 2003). For example, achaete-scute complex (e.g., HASH1) and atonal (ato) homologs (e.g., neurogenin) are required in vivo for development of autonomic and sensory neurons, respectively. By contrast, melanocytes are generated by Wnt signaling, while TGFb promotes smooth muscle cell development. Finally, Notch and neuregulin promote satellite glial and Schwann cell differentiation.

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