The might lose its ability to regulate signaling

The Wnt signaling pathway is a prehistoric biological feature that has been conserved throughout evolution. It is known to play a crucial role in the embryonic development of all kinds of animal species; particularly in the regeneration of tissues in adult of these organisms amongst other many processes. It has also been recorded that mutations and/or deregulated expression of mechanisms of the Wnt pathway is liable to induce disease. And of most importance in the various diseases is cancer. About 25 years ago, the first gene that encodes a Wnt signaling component, Int1, was identified and characterized molecularly from mouse tumour cells. In contrast, the homologous gene Wingless in Drosophila melanogaster, which in known to produce developmental defects in embryos, was characterized. These two scientific breakthrough served as springboard leading to identification and illustration epistatic relationships of further components of the Wnt pathway. It is evident today that Wnt, Notch, Hedgehog, TGF? and a handful of other signaling systems are significant molecular machineries responsible for the control embryonic development. The functions of these signaling systems are beyond cell and tissue boundaries, acting as morphogens that are produced from one cell or tissue type to stimulate surface receptors, signal transduction mechanisms and transcription factors in adjacent cells or tissues, which regulate processes such as cell proliferation, differentiation or survival. As development progresses, the activity of such signaling systems is strongly regulated. In cancer and other diseases however, this regulatory activity could be escaped. In that regard, a signaling cascade supposed to regulate the proliferation, survival of cells might become an oncogene as it undergoes a gain-of-function mutation. Alternatively, an inhibitor might lose its ability to regulate signaling and lose its functions as a tumour suppressor. In either way, as seen in Wnt signaling pathway, are linked to cancer. Therefore, a great deal of effort has been invested globally in developing therapeutic agents that function to improve the Wnt pathway. In addition, a lot of discoveries with regards to Wnt research has covered the spectrum of model organisms, including worms, frogs, mice and even humans and therefore harnessing successful interdisciplinary research.This review is intended for the historical antecedents leading to crucial discoveries about the components and functions of this essential pathway. Special attaention shall be given to Beta?catenin, its identification as part of the wnt signaling pathway, how its overlapping interaction domains for various binding partners allow this signaling to occur, our current knowledge of the various mammalian developmental processes regulated by Beta?catenin and how these could be used for therapeutic purposesHistorical antecedents;In 1982, Roel Nusse and Harold Varmus, reported from the University of California, San Francisco, that a tumour virus induced mammary gland tumours in mice by stimulating the expression of a gene that was initially unknown. This gene, they named Int1. They also speculated that a mutation that causes a loss-of-function in the mouse had occurred, which influences an absence of anterior cerebellum (REF. 2)) this malformation was linked to a mutant allele of Int1 (REFs 3,4). A Drosophila melanogaster mutant without wings, Wingless (Wg), was pronounced in 1973 (REF. 5), with a fly gene which was a homologue of mammalian Int1 (REFs 6,7). The Wg mutation was also associated with segmentation defects in Drosophila embryos. Afterward, the developmental phenotypes were linked to alterations in components of the Wnt signaling pathway. In 1995, the findings on these Drosophila mutants was awarded the Nobel Prize in Physiology. Currently, the term Wnt is an amalgam of Wg and Int10. Pursuant to these findings however, there had been some earlier work on Wnt signaling, in ‘precloning’ times, during which the underlying mechanisms had not been discovered. In the 1930s, laboratory mice were used to establish that, viral insertion can promote mammary tumours (see REF. 11 for an example). Even before this discovery, Mangold and Spemann’s 1935’s Nobel Prize award experiment which was conducted in 1924 which illustrated that a protein which was later known as wnt which was transplanted in the tissue could induce a second body axis, a phenomenon referred to as twin-headed, in newts embryo 12, 13. Moreover in 1902, Morgan, illustrated that   lithium chloride can  also induced double axes in frog embryos through activation of a pathway that was later termed the Wnt signaling pathway14,15.