<b>September 12 2003</b> – Skin, intestinal epithelium, and sperm cell populations are maintained by adult stem cells that strike a delicate balance: always dividing to produce one stem and one cell able to differentiate. Drosophila testes germline stem cells (GSCs) undergoing mitosis always produce one GSC and one gonialblast that subsequently differentiates into a germ cell. This self-renewal process requires a specific microenvironment or niche. In Drosophila, this is provided by a cluster of somatic cells called "the hub," whose local signals maintain GSC identity, but how the niche enables GSCs to strike a balance of renewal and differentiation has been unclear. In the September 12 Science, Yukiko Yamashita and colleagues at Stanford University reveal that intracellular mechanisms involving the centrosome and adenomatous polyposis coli tumor suppressor protein (APC) orient the mitotic spindle perpendicular to the local niche, allowing proper GSC division to occur (Science, 301:1547-1550, September 12, 2003).
Yamashita et al. observed the mitotic spindle in dividing male GSCs through the expression of GFP-&#945;-tubulin and showed that, in all of the cells, the spindle was orientated perpendicular to where the GSCs contacted the hub, in contrast to gonialblasts, where the spindle showed no orientation. The centrosome in early interphase GSCs was also always adjacent to the hub, suggesting centrosome function is important to spindle orientation. They then used centrosomin (cnn) mutants&#8212;cnn is a protein required for normal astral microtubule function&#8212;and observed that in approximately 30% of dividing cnn mutant GSCs the spindle was not orientated, in 10 to 20% association with the cortex near the hub was lost, and in 35% the centrosomes were no longer correctly positioned. These data point to "a specialized region of the GSC cell cortex touching the hub" that provided a positional cue for spindle orientation. The authors then examined the GSC-hub interface and observed DE-cadherin, Armadillo, and APC1/2 to be localized to this region. A mutation in either APC1 or 2 altered spindle orientation, signifying that APCs may be acting as anchors during this process.
"Germline stem cells use intracellular mechanisms involving centrosome function and cortically localized APC to orient spindles perpendicular to the niche, ensuring a reliably asymmetric outcome in which one daughter cell remains in the niche and self-renews" and "the other, displaced away, initiates differentiation," conclude the authors.
<b>Links for this article</b>
F.M. Watt, B.L. Hogan, "Out of Eden: stem cells and their niches," Science, 287:1427-1430, February 25, 2000.
A.A. Kiger et al., "Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue," Science, 294:2542-1545, December 21, 2001.
Y.M. Yamashita et al., "Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome," Science, 301:1547-1550, September 12, 2003.
http://www.sciencemag.org/
Stanford University
http://www.med.stanford.edu/
T.L. Megraw et al., "Zygotic development without functional mitotic centrosomes," Current Biology, 11:116-120, January 23, 2001.
