A modeling approach to study the normal mammary gland growth process.

Terminal end buds (TEBs) are bulb-like structures at the growing tips of elongating mammary ducts, and the growth of a TEB is a complex, organized biological process. In this paper, we present a hybrid continuum-discrete agent-based model to provide quantitative insight into the properties of cell symmetric and asymmetric division on the spatial and developing cell rearrangement within the TEB during ductal elongation. An interplay of endocrine-paracrine signaling and cell lineage has been implemented in the model. Our results show that higher symmetric division rates resulted in more progenitor cells remaining in the TEB, while lower rates resulted in more differentiated cells in the TEB. Moreover, pure proliferation alone was enough to result in ductal elongation in the absence of any cellular migration, a result consistent with current experimental data. This model can also serve as a platform to study how mutation-induced phenotypic changes contribute to developmental defects in mammary gland development.