hiPSC-models of monogenic disorders have begun to facilitate a mechanistic understanding of how genes contribute to disease. Pasca et al (2011) showed that human mutations in the Timothy Syndrome gene Cav1.2 influence calcium signaling and the differentiation of cortical neurons, and the observed defects on calcium (Ca2+) signaling were reversible with the L-type calcium channel blocker roscovitine. Marchetto et al (Marchetto et al., 2010) showed that cultured neurons derived from humans with mutations in the Rett Syndrome gene MeCP2 had fewer synapses, reduced spine density, smaller soma size, and exhibited a reduction in the intracellular calcium response and decrease in the frequency and amplitude of spontaneous excitatory and inhibitory postsynaptic currents.
