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Monday, May 28, 2007

SCIENCE Questions: How Can a Skin Cell Become a Nerve Cell?

"How Can a Skin Cell become a Nerve Cell?" is one of the top 25 questions from the 125th anniversary issue of Science magazine [Science, July 1, 2005]. The complete reference is ...
Vogel, Gretchen (2005) How Can a Skin Cell Become a Nerve Cell 309: 85.
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Gretchen Vogel is a contributing correspondent for Science magazine. She is based in Berlin.

This question is really about developmental biology but it's framed as a question about how (animal) oocytes can reprogram somatic cell nuclei.
Scientists have been investigating the reprogramming powers of the oocyte for half a century. In 1957, developmental biologists first discovered that they could insert the nucleus of adult frog cells into frog eggs and create dozens of genetically identical tadpoles. But in 50 years, the oocyte has yet to give up its secrets.

The answers lie deep in cell biology. Somehow, scientists know, the genes that control development--generally turned off in adult cells--get turned back on again by the oocyte, enabling the cell to take on the youthful potential of a newly fertilized egg. Scientists understand relatively little about these on-and-off switches in normal cells, however, let alone the unusual reversal that takes place during nuclear transfer.
Now developmental biologists may disagree, but I think we pretty much know the answer to this question. Oocytes contain the right transcription factors to activate the genes required for early development. Somatic cells don't have these proteins. When you isolate nuclei from somatic cells and put them in an oocyte you dilute out the various transcription factors than maintained control of gene expression in the differentiated cell. This makes the somatic cell chromatin competent for transcription that's under the control of oocyte factors.

I disagree with Gretchen Vogel when she says, "scientists understand relatively little about these on-and-off switches in normal cells." I think we understand a great deal about the regulation of gene expression. I doubt very much whether there are any mysteries than need to be explained.
Scientists are just beginning to understand how cues interact to guide a cell toward its final destiny. Decades of work in developmental biology have provided a start: Biologists have used mutant frogs, flies, mice, chicks, and fish to identify some of the main genes that control a developing cell's decision to become a bone cell or a muscle cell. But observing what goes wrong when a gene is missing is easier than learning to orchestrate differentiation in a culture dish. Understanding how the roughly 25,000 human genes work together to form tissues--and tweaking the right ones to guide an immature cell's development--will keep researchers occupied for decades. If they succeed, however, the result will be worth far more than its weight in gold.
This is just one more example of confusion about the difference between knowledge and technology. Observing what goes wrong when a gene is mutated has led to huge advances in our knowledge of development. It's fair to say that we understand the basic principles. For some of us that's enough to answer the most important question. But for some Science journalists it's only the beginning. They won't be happy until we can use that knowledge to cure human diseases or repair injuries.

If we were to ask a general question like "What Are the Fundamental Concepts in Development and Differentiation?" then I might agree that it ranks in the top 25 science questions. But this particular question, like so many others, is misguided and anthropomorphic. Furthermore, in terms of fundamental principles, it overlaps extensively with several other questions such as "What Controls Organ Regeneration?", "How Does a Single Somatic Cell Become a Whole Plant?", "What Genetic Changes Make Us Uniquely Human?", and "Can We Selectively Shut Off Immune Responses?"

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