January 02, 2004
Foxg1 Gene Suppression Turns Cortical Cells Into Embryonic Nerve Cells

The Foxg1 gene is necessary for cellular differentiation to produce cerebral cortex cells.

Scientists have identified a gene in the cerebral cortex that apparently controls the developmental clock of embryonic nerve cells, a finding that could open another door to tissue replacement therapy in the central nervous system. In a new study, the researchers found that they could rewind the clock in young cortical cells in mice by eliminating a gene called Foxg1. The finding could potentially form the basis of a new method to push progenitor cells in the brain to generate a far wider array of tissue than is now possible.

The study, led by researchers at NYU School of Medicine, is published in the January 2, 2004 issue of Science magazine.

"What we found was a complete surprise," says Gordon Fishell, Ph.D., Associate Professor in the Department of Cell Biology at New York University School of Medicine. "No one had believed that it was possible to push back the birth date of a cortical neuron. There is this central tenet governing the process of brain development, which says that late progenitor cells [forerunners of mature cell types] cannot give rise to cell types produced earlier in development," he explains.

"Consequently, while some populations of stem cells exist in the adult brain, these cells are restricted to producing only a subset of cell types," notes Dr. Fishell. "If one's goal is to produce cells for replacement therapy, some method must be found to turn back the clock and allow adult stem cells to give rise to the wide variety of cells made during normal brain development."

Eseng Lai, Ph.D., of Merck & Co. and one of the study's co-authors, cloned the Foxg1 gene while he was working at Memorial Sloan-Kettering Cancer Center in New York. He also did seminal work in the late 1990s showing that when the gene is eliminated in embryonic mice, the brain's cerebral hemispheres barely develop. Subsequent work demonstrated that the gene played a role in the early phases of cortical development.

While the press release makes it sound like the researchers have converted more differentiated cells into less differentiated cells my take on this is that what they have really done is found that by knocking out a gene they can prevent nerve stem cells from becoming more differentiated in the first place. They are not converting cells into a less differentiated state. (someone correct me if I'm wrong). They are instead blocking the process of differentiation. That is not nearly as exciting and yet it is a very useful piece of information. But would suppression of the Foxg1 gene in cells that are already more differentiated (more specialized toward becoming neurons of some specific later stage type) cause those cells to revert to a less differentiated state? I don't think these researchers have demonstrated that yet. I also don't think Foxg1 gene suppression in differentiated nerve cells will necessarily cause those cells to revert back into partially differentiated stem cells. The Foxg1 gene might cause methyl groups to be placed in spots on the genome that cause the cells to stay differentiated even once Foxg1 is turned off (just speculating but this is not an unreasonable speculation).

Still, this is useful information. Every discovery of a gene that plays a role in cellular differentiation (the process by which cells become changed to become specialized for specific tasks) provides researchers with useful information that will help point the way toward experiments to attempt that may cause cells to change differentiation state and to revert to some type of stem cells or to convert into a more specialized cell.

There have been a number of recent reports on promising techniques for producing adult stem cells for a variety of purposes. These other reports strike me as more advanced than this latest report excerpted above. See my previous posts Scripps Researchers Find Molecule That Turns Adult Cells Into Stem Cells, TriStem Claims Converts Blood Cells To Stem Cells, and MIT Technique To Produce Large Numbers Of Adult Stem Cells.

There is another angle to this latest report: it may turn out to be useful information for future techniques in intelligence enhancement. If Foxg1 and other related genes can be manipulated to cause more cerebral cortex cells to be made then it may be possible to improve reasoning ability or memory capacity. More generally, research on cellular differentiation and growth regulation of nerve cells will eventually yield information that will be useful for doing intelligence enhancement.

Share |      Randall Parker, 2004 January 02 01:05 PM  Biotech Organ Replacement


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