We developed 3D culture methods that reproduce mammary gland ductal morphogenesis in in vitro conditions. We are proposing a conceptual framework to understand morphogenetic events based on epistemological sound biological principles instead of the common practice of using purely biophysical approaches. More specifically, our theoretical framework is based on the principle that the default state of cells is proliferation with variation and motility. We emphasize the role played by the agency of cells embedded in a gel and the circularity that is relevant for the intended process, whereby cells act upon other cells and matrix elements, and are subject to the agentivity of neighboring cells. This circularity strongly differs from classical linear causality. Finally, our approach opens up the study of causal determination to multilevel explanations rather than reductive ones involving only molecules in general and genes in particular.