DPF is a cell-density sensing factor, with cell-autonomous and non-autonomous functions during Dictyostelium growth and development

Cellular functions can be regulated by cell-cell interactions that are influenced by extra-cellular, density-dependent signaling factors. Dictyostelium grow as individual cells in nutrient-rich sources, but, as nutrients become depleted, they initiate a multi-cell developmental program that is dependent upon a cell-density threshold. We hypothesized that novel secreted proteins may serve as density-sensing factors to promote multi-cell developmental fate decisions at a specific cell-density threshold, and use Dictyostelium in the identification of such a factor.

We have purified a novel secreted protein, DPF, that acts as a density-sensing factor for development and functions to define local collective thresholds for Dictyostelium development and to facilitate cell-cell communication and multi-cell formation. Regions of high DPF expression are enriched at centers for cell-cell signal-response, multi-cell formation, and cell-fate determination. Additionally, DPF has separate cell-autonomous functions for regulation of cellular adhesion and growth.

Dictyostelium grow in the wild as individual cells, but when they become starved for nutrients they are poised to enter a multi-cell developmental program. Multi-cell formation, however, is highly dependent upon cell sufficiency for productive developmental cell-cell communication and aggregation. We have identified the novel protein DPF in Dictyostelium that is secreted by ectodomain shedding and accumulates within the extracellular milieu in parallel with an increasing local cell population. In this manner, DPF serves as a density-sensing factor to correlate the developmental fate switch with the collective local cell population. Regions with the highest DPF concentration preferentially localize at centers for multi-cell formation and additionally determine cell-fate choice. We further demonstrate that DPF also has cell-autonomous functions, most probably associated with the TM/cytoplasmic region. Both segments of DPF, the secreted and the cell-inherent segments, regulate growth and developmental processes.