Neural Crest Gene Expression During Development

More recently in animal studies, a number of genes, including slug, AP-2, HNK-1, and Krox-20,distinguish the earliest neural crest cells from other neighboring epithelial and mesoderm derivatives in normal or genetically modified chicks, frogs, zebrafish, and mice. Many of these genes encode proteins that are thought to regulate gene transcription and neural crest cell determination. These genes are regulated in part by signals induced by bone morphogenic protein (BMP2/4) or Wnts. The BMPs are members of the TGFb signaling path that utilize serine/threonine kinase receptors to transmit extracellular signals to the cytoplasm where a series of intracellular signaling intermediaries (SMADs) relay signals to the nucleus and regulate gene expression. Activation of the Wnt signal transduction path stabilizes the cytoplas-mic protein b-catenin enabling its translocation into the nucleus and activation of neural crest markers (Wu et al. 2003). The BMP alone and in combination with retinoids have been found to induce differentiation of NB tumor cells and control their growth (Y. Nakamura et al. 2003; Sumantran et al. 2003).

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