We review the application of C. elegans as a model system to understand key aspects of stem cell biology. The only bona fide stem cells in C. elegans are those of the germline, which serves as a valuable paradigm for understanding how stem cell niches influence maintenance and differentiation of stem cells and how somatic differentiation is repressed during germline development. Somatic cells that share stem cell-like characteristics also provide insights into principles in stem cell biology. The epidermalseam cell lineages lend clues to conserved mechanisms of self-renewal and expansion divisions. Principles of developmental plasticity and reprogramming relevant to stem cell biology arise from studies of natural transdifferentiation and from analysis of early embryonic progenitors, which undergo a dramatic transition from a pluripotent, reprogrammable condition to a state of committed differentiation. The relevance of these developmental processes to our understanding of stem cell biology in other organisms is discussed.

Highlights d ERK signaling in the Drosophila embryo antagonizes repression in a two-step process d ERK activation leads to rapid loss of a transcriptional repressor from the DNA d Transcriptional repression is reestablished once signal is removed d Signal must persist for proper gene expression and pattern formation

Embryonic development starts with cleavages, a rapid sequence of reductive divisions that result in an exponential increase of cell number without changing the overall size of the embryo. In Drosophila, the final four rounds of cleavages occur at the surface of the embryo and give rise to $6000 nuclei under a common plasma membrane. We use live imaging to study the dynamics of this process and to characterize the emergent nuclear packing in this system. We show that the characteristic length scale of the internuclear interaction scales with the density, which allows the densifying embryo to sustain the level of structural order at progressively smaller length scales. This is different from nonliving materials, which typically undergo disorder-order transition upon compression. To explain this dynamics, we use a particle-based model that accounts for densitydependent nuclear interactions and synchronous divisions. We reproduce the pair statistics of the disordered packings observed in embryos and recover the scaling relation between the characteristic length scale and the density both in real and reciprocal space. This result reveals how the embryo can robustly preserve the nuclear-packing structure while being densified. In addition to providing quantitative description of self-similar dynamics of nuclear packings, this model generates dynamic meshes for the computational analysis of pattern formation and tissue morphogenesis.

A population of Drosophila adult tracheal progenitor cells arises from differentiated cells of the larval main trachea that retain the ability to reenter the cell cycle and give rise to the multiple adult tracheal cell types. These progenitors are unique to the second tracheal metamere as homologous cells from other segments, express fizzy-related (fzr), the Drosophila homolog of CDH1 protein of the APC complex, and enter endocycle and do not contribute to adult trachea. Here, we examine the mechanisms for their quiescence and show that they reenter the cell cycle by expression of string/cdc25 through ecdysone. Furthermore, we show that preventing endocycle entry is both necessary and sufficient for these tracheal cells to exhibit markers of adult progenitors, thus modifying their genetic program. Finally, we show that Hox-mediated regulation of fzr expression is responsible for progenitor identity and thus specifies a group of differentiated cells with facultative stem cell features.