Ca 2+ is a fundamental intracellular signal that mediates a variety of disparate physiological functions often in the same cell. Ca 2+ signals span a wide range of spatial and temporal scales, which endow them with the specificity required to induce defined cellular functions. Furthermore, Ca 2+ signaling is highly plastic as it is modulated dynamically during normal physiological development and under pathological conditions. However, the molecular mechanisms underlying Ca 2+ signaling differentiation during cellular development remain poorly understood. Oocyte maturation in preparation for fertilization provides an exceptionally well-suited model to elucidate Ca 2+ signaling regulation during cellular development. This is because a Ca 2+ signal with specialized spatial and temporal dynamics is universally essential for egg activation at fertilization. Here we use mathematical modeling to define the critical determinants of Ca 2+ signaling differentiation during oocyte maturation. We show that increasing IP 3 receptor (IP 3 R) affinity replicates both elementary and global Ca 2+ dynamics observed experimentally following oocyte maturation. Furthermore, our model reveals that because of the Ca 2+ dependency of both SERCA and the IP 3 R, increased IP 3 R affinity shifts the system's equilibrium to a new steady state of high cytosolic Ca 2+ , which is essential for fertilization. Therefore our model provides unique insights into how relatively small alterations of the basic molecular mechanisms of Ca 2+ signaling components can lead to dramatic alterations in the spatio-temporal properties of Ca 2+ dynamics.