Summary The proliferation/differentiation balance of stem and progenitor cell populations must respond to the physiological needs of the organism [see 1, 2]. Mechanisms underlying this plasticity are not well understood. The C. elegans germ line provides a tractable system to study the influence of the environment on progenitor cells (stem cells and their proliferative progeny). Germline progenitors accumulate during larval stages to form an adult pool from which gametes are produced. Notch pathway signaling from the distal tip cell (DTC) niche to the germ line maintains the progenitor pool [see 3, 4, 5], and the larval germline cell cycle is boosted by insulin/IGF-like receptor signaling [6]. Here we show that, independent of its role in the dauer decision, TGFβ regulates the balance of proliferation versus differentiation in the C. elegans germ line in response to sensory cues that report population density and food abundance. Ciliated ASI sensory neurons are required for TGFβ-mediated expansion of the larval germline progenitor pool, and the TGFβ receptor pathway acts in the germline stem cell niche. TGFβ signaling thereby couples germline development to the quality of the environment, providing a novel cellular and molecular mechanism linking sensory experience of the environment to reproduction.

Members of the subphylum Cephalochordata, which include the genus Branchiostoma (i.e. amphioxus), represent the closest living invertebrate relatives of the vertebrates. To date, developmental studies have been carried out on three amphioxus species (the European Branchiostoma lanceolatum, the East Asian B. belcheri, and Floridian-Caribbean B. floridae). In most instances, adult animals have been collected from the field during their ripe season and allowed (or stimulated) to spawn in the laboratory. In any given year, dates of laboratory pawning have been limited by two factors. First, natural populations of these three most studied species of amphioxus are ripe, at most, for only a couple of months each year and, second, even when apparently ripe, animals spawn only at unpredictable intervals of every several days. This limited supply of living material hinders the development of amphioxus as a model system because this limitation makes it more difficult to work out protocols for new laboratory techniques. Therefore we are developing laboratory methods for increasing the number of amphioxus spawning dates per year. The present study found that a Mediterranean population of B. lanceolatum living near the Franco-Spanish border spawned naturally at the end of May and again at the end of June in 2003. Re-feeding experiments in the laboratory demonstrated that the gonads emptied at the end of May refilled with gametes by the end of June. We also found that animals with large gonads (both, obtained from the field and kept and fed at the laboratory during several weeks) could be induced to spawn in the laboratory out of phase with the field population if they were temperature shocked (spawning occurred 36 hours after a sustained increase in water temperature from 19 degrees C to 25 degrees C).

The intersection between developmental programs and environmental conditions that alter physiology is a growing area of research interest. The C. elegans germ line is emerging as a particularly sensitive and powerful model for these studies. The germ line is subject to environmentally regulated diapause points that allow worms to withstand harsh conditions both prior to and after reproduction commences. It also responds to more subtle changes in physiological conditions. Recent studies demonstrate that different aspects of germ line development are sensitive to environmental and physiological changes and that conserved signaling pathways such as the AMPK, Insulin/IGF, TGFβ, and TOR-S6K, and nuclear hormone receptor pathways mediate this sensitivity. Some of these pathways genetically interact with but appear distinct from previously characterized mechanisms of germline cell fate control such as Notch signaling. Here, we review several aspects of hermaphrodite germline development in the context of “feasting,” “food-limited,” and “fasting” conditions. We also consider connections between lifespan, metabolism and the germ line, and we comment on special considerations for examining germline development under altered environmental and physiological conditions. Finally, we summarize the major outstanding questions in the field.

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SUMMARYThe proper renewal and maintenance of tissues by stem cell populations is simultaneously influenced by anatomical constraints, cell proliferation dynamics and cell fate specification. However, their relative influence is difficult to examine in vivo. To address this difficulty we built, as a test case, a cell-centered state-based computational model of key behaviors that govern germline development in C. elegans, and used it to drive simulations of cell population dynamics under a variety of perturbations. Our analysis provided unexpected possible explanations for laboratory observations, including certain 'all-or-none' phenotypes and complex differentiation patterns. The simulations also offered insights into niche-association dynamics and the interplay between cell cycle and cell fate. Subsequent experiments validated several predictions generated by the simulations. Notably, we found that early cell cycle defects influence later maintenance of the progenitor cell population. This general modeling approach is potentially applicable to other stem cell systems.