Signal flow within intracellular signaling pathways in neurons is known to be compartmentalized. Signals are dynamically controlled in local regions (microdomains) within the dendrite and cell body, although many signaling components can diffuse through the cell body and dendrites. The mechanisms underlying the formation and dynamics of microdomains are not well understood. In addition, it is not clear how spatial information is transmitted from upstream to downstream components within a signaling network. We have computationally studied the various factors responsible for local signaling and the flow of spatial information in neurons. For this we have used the β-adrenergic receptor cAMP/protein-kinase A/ b-Raf/MAP-kinase signaling network that consists of a negative feedback loop stacked on top of a feedforward loop when signal flows from the receptor to MAP-kinase 1, 2. Numerical simulations of partial differential equation models of this network using realistic cell shapes were conducted in the Virtual Cell. Cell shape and surface-to-volume ratios play important roles in the origin of microdomains of upstream signaling components of this network. For transmission of spatial information, cell shape serves as a constraint for local activity of negative regulators, such as phosphodiesterases and protein phosphatases to control information from cAMP to MAP-kinase. While information regarding the activation state is transmitted through the stimulatory arm of the feedforward motif, the spatial information is transmitted through control of the negative regulator of MAPK1,2. Predictions that an upstream negative regulator controls the propagation of spatial information to downstream components were verified experimentally in rat hippocampal slices. We conclude that cell shape-constrained local reaction balance within stacked regulatory loops propagates spatial information through signaling networks.