The Drosophila germline lineage depends on a complex microenvironment of extrinsic and intrinsic factors that regulate the self-renewing and asymmetric divisions

Stem cells in adult tissues share two defining characteristics – cell division is self-renewing and asymmetric. In the Drosophila oogenic germline, the self-renewing aspect of the division produces a new stem cell that remains associated with a complement of somatic cells (terminal filament cells, cap cells and inner sheath cells; collectively, somatic tip cells) that maintain a supportive microenvironment (Spradling et al., 2001). Parallel investigations of the fly’s spermatogenic lineage have revealed that a morphologically similar but molecularly distinct microenvironment supports spermatogenic stem cells (Tulina and Matunis, 2001; Kiger et al., 2001). Studies from several laboratories have identified genes required in ovarian somatic tip cells that are necessary for germline stem cell (GSC) function, including piwi, dpp and fs(1)Yb (Cox et al., 2000; King and Lin, 1999; Xie and Spradling, 1998). Genes required within the GSCs include nanos (nos), pumilio (pum) and the Dpp-dependent receptors and transcription factors (Forbes and Lehmann, 1998; Lin and Spradling, 1997; Xie and Spradling, 1998). Asymmetry of the GSC division produces a specialized cystoblast that will produce a clone of cells from which the oocyte proper will form. Mutations in such genes as pum or nos destroy asymmetry because both daughters differentiate as cystoblasts, causing the loss of GSCs (Forbes and Lehmann, 1998; Lin and Spradling, 1997). The opposite is true when cystoblast differentiation factors, such as bam or bgcn, are inactivated. In these cases, asymmetry is disrupted because both GSC daughters retain GSC characteristics (Gateff, 1982; Lavoie et al., 1999; McKearin and Ohlstein, 1995; McKearin and Spradling, 1990). The cystoblast is a differentiated cell because, unlike the GSC, it divides precisely four times to produce 16 daughter cystocytes, which eventually produce 15 nurse cells and one oocyte. Also, unlike the GSC, each cystoblast or cystocyte cell division executes only partial cytokinesis and thus the cystocytes remain interconnected as a cyst (de Cuevas et al., 1997). Fig. 1 presents a schematic view of germarial Region 1 (the cyst-forming region) on which the pattern of bam mRNA and protein accumulation is superimposed. Low levels of Bam protein are expressed in GSCs, where it accumulates in fusomes but bam mRNA is undetectable by in situ hybridization. These observations indicate that bam is transcribed at a very low level in GSCs and that this small amount of transcript produces the protein seen associated with GSC fusomes. In the cystoblast and young cystocytes, bam transcripts become readily detectable, reflecting an upregulation in transcription rate or increased stability of the mRNA. This more abundant pool of mRNA produces higher levels of Bam protein that begin to accumulate in the germ cells’ cytoplasm and continues to decorate the growing fusome (McKearin and Ohlstein, 1995). As cysts mature, the abundance of bam transcripts declines such that mRNA is again undetectable in eight-cell cysts and Bam protein levels 1159 Development 130, 1159-1170 © 2003 The Company of Biologists Ltd doi:10.1242/dev.00325