Notch Signaling, Essay Example

The Notch gene was first discovered by Thomas Hunt Morgan in 1917.  It was Morgan, that first noticed in the strain of the fruit fly  notches appeared in their wing blades.  The Notch protein is considered to sit like a trigger, which spans the cell membrane.  Hence the Notch signaling pathway is a highly conserved cell signaling system, which can be found present in most multicellular organisms.  The Notch receptor has been described as a single pass, transmembrane receptor protein.  This is related to notch ligands  which are also transmembrane proteins.

The function of the Notch signaling pathway is considered important for cell to cell communication.  This is the gene regulation mechanisms that control the multiple cell differentiation processes, typically during embryonic and adult life.  Not signaling has been discreetly laid it in many cancers and 14 not signaling has been implicated across a considerable number of diseases, which include: lymphoblastic leukemia, multiple sclerosis, dominant Arteriopathy etc..

So in summary, the Notch can be described as a transmembrane receptor mediates local cell to cell, communication.  It is this signaling cascade, which is present in all animal species which have been studied to date.  The concept of Notch signaling has been widely used to determine the fate of cells and to regulate the pattern formations.  The dysfunction of these create a considerable variety of developmental defects and adult pathologies.  In biology, the ability to form these patterns is considered key to the orderly and reproducible development of all multicellular life. ” Notch is an unusual protein in that it functions both at the cell surface.  To receive extracellular signals, and in the nucleus to regulate gene expression.”  (Lai, 2004).

The early origin of Notch signaling, originated in studying fly embryos; these exhibiting excessive neuronal differentiation.  The term neurogenital phenotype continues to be used today in order to identify new genes that are effectively connected to Notch signaling is a concept.  As such.  She describes a loss of function condition.  The basic operation of the Notch pathway comprises three  key players, 1) Delta-type ligand  2) .  The receptor Notch, and 3) .  The CSL  transcription factor.  Guilt and Notch off-chance membrane proteins, each containing extracellular arrays of EGF repeats.  The activation of the Notch by its ligand  triggers two proteolytic cleavages of notch.

During the early 1990s.  It was suggested that Notch is cleaved join the Notch signaling process.  This resulted in Notch proteolysis be far more complicated than originally envisaged.  This being taking a significant in the study of Alzheimer’s disease.  Another aspect of Notch signaling is that it specifies cell fates and creates boundaries.  This is where the Notch is seen to promote the development of a given cell type or body region, by the use of acting regulate free molecules .  During this process, not signaling creates a new cell type, and as such, results in a cell to cell interaction at the boundary between distinct cell populations.

The actual concept, the Notch pathway leads us to consider the straightforward signal cascade and equally with straightforward consequences on gene expression as a result.  However, in reality, this is much more intricate and complicated.  The combined regulation of Notch target genes.  He seemed to produce unexpected consequences.  Biologists have also noted that Notch signaling has a considerably to the two amplify small differences contained within the signaling capacities of different cells.  Notch signaling has been used in this study and development of neural behaviour.  And given the widespread role of Notch signaling.  It became clear that deviant patterns underlie some human diseases.  Aberrant Notch signaling has also been identified in several human cancers.  The chromosomal rearrangement of the cells illustrates constitutive Notch activity of T cells.  Most often associated with skin and corneal tumours.  Other cancers such as cervical and prostate cancer have been correlated with alterations in the expression of the Notch protein ligand.  These biological observations suggest a broader role for Notch dysfunction in cellular transformation studies.  Looking forward, scientists hope that improved knowledge of the mechanism of Notch signaling will result in better understanding of therapeutic design.  At the moment considerable study and experimentation is being carried out on mice.  Biologists believe Notch signaling to be an example of a particular successful signaling cascade that is repeatedly used during the development of all metazoan organisms.

Given the development of Notch signaling in animal development.  There is also an evolutionary concept.  How did this signaling concept originally assemble during stages of evolution? ” The signals that pass between cells are far simpler than human messages: typically a particular type of molecule is produced by one cell signalling cell and detected by another the target cell, by means of a receptor protein which recognises and responds to the signal molecule ”  (Alberts, 1997).

Notch signalling plays an important role in haematopoiesis.  Recent research studies showed Notch signalling has been a critical factor involved in the maintained in its old self renewing hematopoietic stem cells.  The inhibition of Notch signalling appears to enhance HSC differentiation in vitro and in vivo.  In addition to maintaining HSC population in Notch signalling would seem to be involved in the maintenance of uncommitted population of  lymphoid, myeloid and erythroid precursor populations.  Owing to this important role in Notch signalling these to be precisely regulated, as deregulated expressions of not pathway elements can lead to development of haematological malignancies.  As Notch signalling has the ability to regulate the differentiation fate of individual cells.  It has been ultimately involved in the development of numerous tissues in multicellular organisms.  Notch signalling is also seem to play a role in the development of tissues which are derived from three primary germ layers i.e. endoderm, mesoderm, hematopoietic system , mammary gland and vasculature.

More recent research studies have indicated a potential role for Notch signalling in human breast cancer development.  The overactive expression of consecutively active Notch all in human breast cells induced transformation in vitro.  A study involving seven breast cancer specimens found Notch one protein expression to be detected in all tumours that were examined.  A further study involving the research of 97 specimens further demonstrated that poorly differentiated breast tumours had association with elevated levels of Notch one protein and subsequently reduced patient survival.  Continuation of the research showed that 50% of human breast tumours expressed reduced protein levels of numb, the negative regulator of Notch signalling.

Notch pathways have also been observed in solid human tumours i.e., hematologic malignancies.  The vast majority of the studies have indicated correlation associations between the notch ligand and the receptor expression for tumour development.  Change  to protein over expression was reported to be seen in human pancreatic cancer and expression  in human cervical cancer samples and indicated that both mRNA and protein levels in brain cancer.  Of all of the cancer related studies the most extensive research has been carried out in breast cancer, and in particular, using  mouse samples. (Kevin G. Leong, 2005)

Works Cited

Alberts, B. (1997). Molecular Biology of the Cell. New York: Garland Publishing.

Kevin G. Leong, a. A. (2005). Recent insights into the role of Notch signaling in tumorigenesis. American society of hematology , 2223-2233.

Lai, E. C. (2004). Notch Signaling: control of cell communications and cell fate. Howard Hughes Medical Institute , pp. 965-973.