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Notch 1

NOTCH REGULATES CELL DIFFERENTIATION AND TISSUE DEVELOPMENT
Notch 1 is a technology that regenerates musculature, heart tissue, and neuronal tissue. A hallmark of aging is diminished regenerative potential of human musculature. The mechanism of this decline is now known. Analysis of injured muscle revealed that, with age, resident precursor cells (satellite cells) had a markedly impaired propensity to proliferate and to produce myoblasts necessary for muscle regeneration. Sufficient up-regulation of a special receptor ligand results in muscle, neuronal, and heart tissue regeneration in old musculature.

Notch signaling plays an integral role in the differentiation of a variety of cell lineages. Originally described as a mechanism for the inhibition of cell differentiation, the Notch signaling pathway was believed to maintain cells in an undifferentiated state, thus allowing cells to respond to inductive cues at appropriate times to facilitate cellular diversification. Indeed, Notch signaling has been shown to inhibit T-cell development, granulocytic differentiation, neurogenesis, and myogenesis. This view of Notch function, however, proved to be oversimplified, as Notch signaling has also been shown to direct cells toward alternate differentiation fates, for instance during gliogenesis. Thus Notch signaling can either block or promote cell differentiation, depending on the cell lineage.

Because of its ability to regulate the differentiation fate of individual cells, Notch signaling is intimately involved in the development of numerous tissues in multicellular organisms. In mammalian embryos, Notch receptors and ligands are widely expressed during organogenesis and indeed, play a role in the development of tissues derived from all 3 primary germ layers: endoderm (eg, pancreas), mesoderm (eg, hematopoietic system, mammary gland, vasculature), and ectoderm (eg, nervous system).

In addition to regulating embryonic tissue development, Notch signaling also controls fetal and postnatal tissue development, as well as the development and maturation of adult tissues. Hence precisely controlled Notch signaling is vital to the proper development of most tissues. Accordingly, perturbation of Notch signaling can manifest as tissue abnormalities ultimately leading to disease states such as cancer.