Several other studies 80–86 have also studied the morphology of hiPSC-derived neuronal progenitors and/or neurons from RTT patients with MECP2 mutations. Many of these of have largely corroborated the results of Marchetto et al., showing small cell body size, deficits in neuronal maturation, and decreased dendritic complexity. Djuric et al 86, went on to also show that RTT neurons had decreased cell capacitance, dysfunction in action potential generation, dysfunction in voltage-gated sodium currents, and dysfunction in miniature excitatory synaptic current frequency and amplitude. Two studies demonstrated particularly well the power of hiPSCs by showing that RTT neurons had a delayed functional switch in GABA from excitatory to inhibitory 84 and neuronal progenitors from RTT patients had an increased frequency of L1 retrotranspositions 83, conclusions almost impossible to derive from any other experimental medium. Tang et al. went on further to show that IGF1 treatment rescued GABA functional deficits 84. In addition, Rett gain of function by gene duplication (MECP2dup) has also been modeled in hiPSC lines, showing a phenotype in many respect opposite to that of Rett loss of function, namely increased synaptogenesis and dendritic complexity along with altered neuronal network synchrony 73.
