Stem cell maintenance in multilayered shoot apical meristems (SAMs) of plants requires strict regulation of cell growth and division. Exactly how the complex milieu of chemical and mechanical signals interact in the central region of the SAM to regulate cell division plane orientation is not well understood. In this paper, simulations using a newly developed multiscale computational model are combined with experimental studies to suggest and test three hypothesized mechanisms for the regulation of cell division plane orientation and the direction of anisotropic cell expansion in the corpus. Simulations predict that in the Apical corpus, WUSCHEL and cytokinin regulate the direction of anisotropic cell expansion, and cells divide according to tensile stress on the cell wall. In the Basal corpus, model simulations suggest dual roles for WUSCHEL and cytokinin in regulating both the direction of anisotropic cell expansion and cell division plane orientation. Simulation results are followed by a detailed analysis of changes in cell characteristics upon manipulation of WUSCHEL and cytokinin in experiments that support model predictions. Moreover, simulations predict that this layer-specific mechanism maintains both the experimentally observed shape and structure of the SAM as well as the distribution of WUSCHEL in the tissue. This provides an additional link between the roles of WUSCHEL, cytokinin, and mechanical stress in regulating SAM growth and proper stem cell maintenance in the SAM.