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Name: Angela
Status: other
Grade: other
Location: CA
Country: USA
Date: N/A 


Question:
How do cells limit gene expression?



Replies:
I am not completely sure what you intend by your question, and it could refer to so very many aspects of genetic controls that are in play with regard to development as well as any other cellular activity at any point in the development of a fertilized egg to an adult of whatever species of plant, animal, or microbe. I thought I would provide an insight on gene expression provided years ago by one of the great molecular biologists: Nobel Laureate and Professor Sydney Brenner of Cambridge University, UK. Prof. Brenner did his Nobel prize-winning work on unraveling the genetic code using the bacterium E. coli, and discovered how it was that particular triplets of nucleotides in the DNA of an organism's genome are translated into the individual amino acids of the organism's proteins. Later, Prof. Brenner chose to work on a small animal that eats the very microbe on which he did his earlier work, the nematode worm C. elegans. He wanted to understand what occurs in the development of a fertilized egg on its way to becoming an adult, and C. elegans having about 1000 cells as an adult, easily grown in the lab, easily crossed between individual worms having differing phenotypes, able to be raised at different temperatures, and more made it a great system of study for learning principles of development.

Among many questions of development that were open questions was how it was that the fertilized cell gives rise to all of the differentiated cells ofthe adult - at what point does the fertilized cell's totipotency (I.e., having ability to form any cell type, accessing any of its genes) become of narrower capability, to omnipotency capable of giving rise to a subset of the animal's cells by its daughter cells, to only giving rise to a terminally differentiated cell whose daughter cells will only be that one cell type. It was believed then as it is now that these variant capabilities are determined by the genes that are active and not active at differing points in the organism's development. But what signaled what genes are on or off, or as we now know, what form is the gene or its messenger taking to express the category of the gene itself - this really is complicated stuff. Well, at a lecture in 1976 in Berkeley, Prof. Brenner revealed one of those aphorisms I've not forgotten: What genes are enlisted in development, indeed development itself, includes two basic mechanisms by which the totipotent early stage cells divide and provide generations of daughter cells that form an adult. One mechanism was called the British plan where the cell's development, the sets of genes in play, were determined based on the parentage of each set of daughter cells. Clearly, that is not sufficient because you'd never have the differentiated cells arise, and of course they do. Basing the next mechanism's descriptors on ablation studies where individual cells in early stage worm embryos are specifically killed to see how the remaining cells recover or not (an experimental approach first shown in the early 20th C by Spemann and others), Prof. Brenner described the American plan that is key to development and gene expression. In the American plan, different sets of genes are expressed, and development ensues, as a function of what other cells or signals, chemicals that is, are in the neighborhood.

There you have it: gene expression giving rise to all the differentiated cells of an adult based on who was the earlier cell's daddy and who and what were the neighbors!

Don Silvert


Angela,

Gene expression can be limited by miRNA (microRNA), also called siRNA (small interfering RNA), which are complementary sequences that bind to targeted mRNA which result in Gene Silencing.

-Alex Viray



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