Stem cells are characterized by their ability to self-renew and to produce numerous differentiated daughter cells. This special ability enables stem cells to play a central role in generating and maintaining many tissues during development. We have established Drosophila germline stem cells (GSCs) as an effective model for studying asymmetric stem cell divisions.
A transplantation technique combined with laser ablation identified GSCs in the Drosophila ovary. These stem cells undergo self-renewing asymmetric divisions that generate a daughter GSC and a differentiated daughter. The divisional asymmetry is marked and controlled by the asymmetric segregation of a novel centriole-associated "organelle" termed the spectrosome, as well as by interactions with nearby somatic cells.
The spectrosome, containing abundant membrane skeletal proteins, anchors the mitotic spindle and localizes factors important for GSC division. Pumilio (pum) and bgcn mutations affect the spectrosome structure and often abolish the asymmetry of GSC division, leading to the formation of numerous stem-like tumorous germ cells. In contrast, piwi and fs(1)Yb mutations affect GSC self-renewal, while arrest mutations appear to block both GSC division and differentiation. Pum and arrest encode translational suppressors, indicating the involvement of the translation regulation mechanism in GSC division, while piwi and fs(1)Yb encode novel proteins.
We identified piwi-interacting genes by genetic suppressor screens. We also cloned piwi homologs in C. elegans, mouse, and human; identified pum homologs in C. elegans and human; and piwi-like genes in Arabidopsis known to be required for meristem cell maintenance. Decreasing the expression of piwi homologous genes in C. elegans significantly reduces the proliferation of GSC-equivalent cells. Our analysis of these genes in diverse organisms has started to reveal a mechanism of stem cell division that is well conserved during evolution.
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