Translational control in germline stem cell development

Abstract

Stem cells give rise to tissues and organs during development and maintain their integrity during adulthood. They have the potential to self-renew or differentiate at each division. To ensure proper organ growth and homeostasis, self-renewal versus differentiation decisions need to be tightly controlled. Systematic genetic studies in Drosophila melanogaster are revealing extensive regulatory networks that control the switch between stem cell self-renewal and differentiation in the germline. These networks, which are based primarily on mutual translational repression, act via interlocked feedback loops to provide robustness to this important fate decision.

Figure 1.

Adult Drosophila ovary. (top) Schematic drawing of a germarium and an egg chamber. Somatic tissues are shown in pink, and germline tissues are shown in blue. (bottom) Immunostaining of a germarium. Blue, anti-Vasa antibody (germ cells); green, anti-GFP antibody showing gfp expression under control of the bam promoter expressed in CB and cysts (note that endogenous Bam protein expression is spatially even more restricted than the GFP expression shown); red, anti-Hts (Hu li tai shao) antibody marks spectrosomes in GSCs and CBs, fusomes in multicellular cysts, and membranes in somatic follicle cells. Anterior is to the left.

Figure 2.

Gene regulatory networks controlling GSC self-renewal and differentiation. (A) Self-renewal network active in GSC. (B) Differentiation network active in differentiating cells, i.e., cystoblasts (CBs) and cysts. Self-renewal factors (blue) and differentiation factors (green) operating in each cell type are shown in the darker color, and the inactive factors are shown in light blue/green. Arrows illustrate positive and negative regulatory interactions. Numbers on the arrows are described throughout the text. E-cadh, E-cadherin; Pelo, Pelota; Tkv, Thickvein; Udd, Under-developed.

Figure 3.

Expression patterns in germ cells in germaria. (left) For each gene and for the phosphorylated Mad protein (pMad), changes in protein levels (high or low) are depicted during the indicated stages. (right) RNA expression patterns are summarized. Note that protein patterns are dynamic, whereas there is little change in RNA expression with the exception of bam.

Figure 4.

Examples of network modules. (A) Transient and spatially highly restricted expression of Bam provides a gate into differentiation. Markers for image shown are same as in Fig. 1. (B) Examples of interlocked double negative gates that result in positive feedback loops when one component in the network increases or decreases. Proteins promoting stem cell fate are shown in blue, and those promoting differentiation fate are shown in green. (C) Nos–Pum and Brat–Pum complexes inhibit each other by competing for Pum binding.