Collective Growth in a Small Multicellular Structure

Abstract

All living cells must regulate their size and shape. Studies of single cell systems have identified key signaling pathways and molecular actors that orchestrate these complex processes. Yet progress in our understanding of growth regulation in multicellular systems has lagged. This work establishes the Drosophila melanogaster egg chamber as a simple, yet powerful model system for mechanistic studies of collective growth phenomena in a multicellular context. We found that throughout oogenesis, both tissues comprising the Drosophila egg chamber grow dramatically, through cell division and without, and do so nonuniformly. In the germline cluster, 16 cells diverge in size in a predictable manner due to asymmetric transport through arrested cleavage furrows known as ring canals. In the overlying somatic epithelium, it is clone sizes that diverge. In this tissue, cell of a lineage also remain connected through ring canals that facilitate diffusion, and clones grow through propagation of local mitotic waves. Both tissues grow jointly and exhibit collective growth phenomena at the tissue-level, yet both can be visualized and studied mechanistically, with single cell resolution. We also report on findings that are tangentially related to growth regulation, but arose naturally from studying ovarian development in Drosophila. We have found that the three-dimensional arrangement of the 16 cells in the germline cluster within its epithelial enclosure is highly diverse, and that entropic constraints favor particular configurations. Furthermore, our studies of oocyte selection reveal that the early localization and autoregulatory activity of a particular oocyte fate determinant are critical for cell fate specification and maintenance. In all projects, we combined experiments, microscopy and image processing, and theory to address basic biological questions in a highly tractable experimental system. Our work adds to the expanding repertoire of known mechanisms and model systems in the realm of growth regulation, and brings the field a step closer to a more quantitative and predictive understanding of these processes in a uniquely suited multicellular experimental system.