Modeling the Canalizing Effects of the Delta-Notch Signaling Pathway.

Canalization is a biological framework for describing the patterned development of adult tissues from a set of un-patterned natal tissues through local interactions that produce global effects. An Agent-Based Model (ABM) of the Delta-Notch signaling pathway has been developed that organizes at the protein-level to exhibit selection effects at the cellular-level. The Delta-Notch signaling interaction is a well understood developmental patterning mechanism first elucidated in Drosophila but utilized in most developing organisms. The model focuses on the active agents of the signaling pathway, Delta (Dl) and Notch (N), which are initially generated by a producer agent. The space is enclosed by agents representing the outer-membrane, where both signaling agents are localized and diffuse within after production. The membrane placement allows signaling agents of neighboring cells to interact; this interaction produces a cleaved N that acts to alter the production of the signaling pathway agents Cells within the model are driven towards a neuronal or epidermal cell fate, forming a rosette pattern where each neuron is surrounded by only epidermal cells and identical to the patterning seen in the biological system. As the model is executed, the system will go through repeated periods where structure is constructed and then destructed, ultimately developing larger regions of rosette cell patterning with each cycle. This behavior is derived from fine-grained spatial information established by the cellular movement of the agent, allowing for ad-hoc signal regionalization.