Cell differentiation is the process by which stable differences arise between cells. All higher organisms develop from a single cell, the fertilized ovum, which gives rise to various tissues and organ.
Cell differentiation leads to distinguishable cell types whose character and properties are determined by their pattern of gene activity and the proteins they produce. Transplantation of nuclei from differentiated animal cells into fertilized eggs and cell fusion studies show that the pattern of gene expression in the nucleus of a differentiated cell can often be reversed, implying that it is determined by factors supplied by the cytoplasm and that no genetic material has been lost.
Although the differentiated state of an animal cell in vivo is usually extremely stable, some causes of differentiation are reversible. Tran differentiation of one differentiated cell type into another type has been shown to occur during regeneration and in cells in tissue culture.
In many cases, the pattern of gene activity is under continuous control. Maintenance and inheritance of a pattern of gene activity may involve several mechanisms, including the continued action of gene regulatory proteins; changes in the packing state of chromatin, and chemical modifications to the DNA.
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(A) Cytoplasmic determinants:
Nuclear transplantation experiments in frog have shown that the genome remains constant during cell differentiation. Cytoplasm contains substances called ‘determinants’ that become unequally distributed among embryonic cells and cause them to follow a particular differentiation pathway.
The best example of cytoplasmic determinants is provided by the granules present in germ cells. When they are centrifuged or transplanted into different positions, they will induce the formation of germ cells in a different position.
In early embryos, rate of cell division is very fast and during this period there is no RNA synthesis, but when the 4000-cell stage (called-mid-blastula transition) is reached, synthesis of most types of RNA starts simultaneously.
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(B) Molecular Differentiation:
How is a gene expressed in certain tissues and not in others? It seems that not one but multiple mechanisms are used. Activation of transcription is probably the most common one, used in many protein-coding genes, e.g. globin in red blood cells, ovalbumin in oviduct & silk fibroin in the silk gland. Exactly how this is achieved is not known.
Chromatin structure and DNA methylation have been explored as possible mechanisms. Translational control is known to occur is some eggs that have “marked” m RNAs that are translated only after fertilization. The best example of translational control is provided by the heat shock m RNA of Xenopus oocytes, which are stored but not translated unless the temperature is raised.
In gene amplification specific genes are selectively replicated to attain a higher level of expression. Gene amplification happens with r DNA in some oocytes, the DNA puffs of Rhynocosciara, and with the chorion (egg shell) genes of Drosophila. It is a rare event, and in all cases the amplified DNA is not passed on to future cell generations.
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Transposition of genes form a ‘silent’ site in the chromosome into an ‘expression site’, where they are actively transcribed, occurs in the yeast mating type switch and in trypanosomes that change periodically their surface antigens as a defense against the host’s immune system. Transposition is known not to occur for globin, ovalbumin and many other genes.
The production of antibodies by B- lymphocytes is the best example of how intricate the control of cell differentiation might be. Initially, variable region DNA is brought close to a constant region by a DNA deletion.
A membrane-bound antibody molecule is initially produced but upon stimulation with antigen, the cell starts secreting antibody by a mechanism controlled at the RNA processing level. Finally another DNA deletion might bring the same variable region closer to a new type of constant heavy chain, producing different types of immunoglobulins (IgG, Ig E, IgA).
It is possible in adult tissue mechanisms similar to those of cytoplasmic determinants in embroyes might operate. For example, when cytoplasmic components become unequally distributed among daughter cells, one cell may become differentiated while the other remains as a stem cell.
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The differentiation of the various lineages seems to depend on external signals, although there is evidence for autonomous diversification, and external factors are essential for survival and proliferation of specific cell types. Similar processes also occur in the diversification of neural crest.
Before migration, single crest cells have a broad developmental potential, and environmental signals can both direct the pathways of neural crest differentiation and promote survival of particular cell types. Programmed cell death is common fate for cells, especially during development and there is evidence that positively acting signals are generally required to prevent programmed cell death and allow cells to continue to survive.