February 27 2006
9:30 LSB 2320

Abstract:

Stem cells are the source of highly-differentiated but short-lived cells such as blood, skin and sperm. When stem cell divides, stem cell must make a choice between alternate cell fates; self-renewal of stem cell identity or commitment to differentiation. The balance between these two alternate fates is crucial for tissue homeostasis. To maintain this balance, stem cell has a potential to divide asymmetrically, producing one self-renewed stem cell and one differentiating cell. The Drosophila male germ line provides an excellent model system in which to study asymmetric stem cell divisions. In adult male testes, 8-10 germ line stem cells (GSCs) surround a cluster of somatic cells, called hub. The hub functions as the niche for GSCs by secreting a signalling ligand, unpaired (Upd), to activate the JAK-STAT pathway in GSCs to specify stem cell identity.
We have shown that GSC orients its mitotic spindle perpendicularly toward the hub such that one daughter cell remains attached to the hub and maintains stem cell identity, while the other is displaced away from the hub and initiates differentiation, thereby ensuring the asymmetric outcome of the division. Stereotyped positioning of the centrosomes during interphase plays crucial role in orienting mitotic spindles of GSCs toward the hub: One centrosome is always positioned close to the hub, while the other centrosome migrates toward the opposite side of the nucleus during interphase, thereby preparing the perpendicular orientation of the mitotic spindle. We have proposed that the centrosome close to the hub is anchored to the adherens junctions, which are formed between GSCs and the hub, via astral microtubules and apc2 tumor suppressor. Recently, we found that the mother centrosome stays close to the hub, while the daughter migrates, suggesting that physical difference(s) between mother and daughter centrosomes are utilized to achieve stereotyped behavior of centrosomes to orient GSCs with respect to the niche. In summary, cellular mechanisms that orient GSCs with respect to the niche play a fundamental role during asymmetric stem cell division.