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On the hunt for Foxd3’s role
Realizing the promise of stem cells as clinical therapeutics will require a full understanding of the factors that maintain these unique cell populations. Patricia Labosky, Ph.D., and colleagues have been tracking the role of one such factor, Foxd3. They previously showed that Foxd3 is required early in mouse development for establishing both the stem cells that build the embryo and those that form supportive tissues like the placenta.
Now, the investigators report in the May 1 issue of Development that Foxd3 also is required to maintain neural crest cells – a population of progenitor cells that migrate through the developing embryo and contribute to a wide variety of adult tissues. Mice with a deletion of the Foxd3 gene in neural crest cells die shortly after birth with a catastrophic loss of neural crest-derived tissues. The findings support the idea that the self-renewal mechanisms that maintain stem cell populations are conserved among different types of progenitor cells.
— Leigh MacMillan
The long and short of telomeres
Reminiscent of the plastic tips on shoelaces, telomeres – the short, repetitive bits of DNA at the ends of chromosomes – protect the ends of DNA from degradation. The length of telomeres, which is maintained by the enzyme telomerase, dictates how many times a cell can divide, and so has important implications for cancer and aging.
Katherine Friedman, Ph.D., and colleagues previously discovered several mutations in one telomerase subunit, called Est2p, that result in abnormally long telomeres in the yeast Saccharomyces cerevisiae. In the April issue of Molecular and Cellular Biology, the investigators show that some of these mutations reduce the association of telomeric DNA with another protein, Rap1p, whose binding normally reduces telomerase activity and prevents telomere elongation. The decreased association of Rap1p with telomeric DNA did not depend on altered telomere sequence, suggesting that telomerase can either directly or indirectly modulate the binding of Rap1p to telomeric DNA. The results provide insight into how telomerase keeps telomere length “just right.”
— Melissa Marino
Myelin formation – that’s a wrap
In the peripheral nervous system, myelin – the insulating sheath around nerve axons – is formed by the tight wrapping of Schwann cells around the axons. Physical contact between Schwann cell precursors and the axon induces this process, but the mechanisms that prompt immature Schwann cells to differentiate into their mature, myelinating forms are unclear.
Previously, Bruce Carter, Ph.D., and colleagues showed that the transcription factor, nuclear factor kB (NF-kB), is required for myelin formation. In the April 2 issue of The Journal of Neuroscience, the investigators reveal crucial steps between neuron-Schwann cell contact and NF-kB activation. Graduate student Choya Yoon found that cell-cell contact causes a chemical modification of an NF-kB subunit, increasing its activity in cultured cells and developing rat sciatic nerves. Genetically altering NF-kB to prevent this modification inhibited Schwann cell differentiation, reducing the number of myelinated fibers in cultured cells by 45 percent. Since a common type of inherited nerve disorder, Charcot-Marie-Tooth disease, is caused by the disruption of peripheral myelin formation, this pathway could represent a new therapeutic target.
— Melissa Marino
Making radiation more deadly
Tumor blood vessels – the “supply lines” that support cancer growth – are inherently resistant to the toxic effects of radiation. A protein that could contribute to this resistance is bone marrow X kinase (Bmx), which is involved in cell growth and survival pathways in a variety of cell types, including blood vessel endothelial cells.
Christopher Willey, M.D., Ph.D., and colleagues report in the April 15 issue of Cancer Research that clinically relevant doses of radiation rapidly activate Bmx in cultured human endothelial cells. They showed that pre-treating the cells with small RNA molecules that reduce Bmx levels or with a drug that inhibits Bmx activity enhanced radiation’s cell-killing effects. In mouse lung cancer models, radiation in combination with the Bmx inhibitor destroyed tumor blood vessels and delayed tumor growth more than radiation or drug alone. The findings support the idea that Bmx promotes a cell survival pathway in endothelial cells and suggest that blocking its activity may improve the effectiveness of radiation therapy.
— Leigh MacMillan
Past Aliquots
June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012