Characterizing PCDH19 in human induced pluripotent stem cells (iPSCs) and iPSC-derived developing neurons: emerging role of a protein involved in controlling polarity during neurogenesis

// Claudia Compagnucci 1 , Stefania Petrini 2 , Norimichi Higuraschi 3 , Marina Trivisano 4 , Nicola Specchio 4 , Shinichi Hirose 3 , Enrico Bertini 1 and Alessandra Terracciano 1 1 Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy 2 Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy 3 Central Research Institute for the Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan 4 Division of Neurology, Bambino Gesu Children’s Hospital, IRCCS, Rome, Italy Correspondence to: Alessandra Terracciano, email: // Keywords : PCDH19, human iPSCs, iPSC-derived neurons, neuronal polarity, neural rosettes, Neruoscience Section Received : July 30, 2015 Accepted : September 05, 2015 Published : September 21, 2015 Abstract PCDH19 (Protocadherin 19), a member of the cadherin superfamily, is involved in the pathogenic mechanism of an X-linked model of neurological disease. The biological function of PCHD19 in human neurons and during neurogenesis is currently unknown. Therefore, we decided to use the model of the induced pluripotent stem cells (iPSCs) to characterize the location and timing of expression of PCDH19 during cortical neuronal differentiation. Our data show that PCDH19 is expressed in pluripotent cells before differentiation in a homogeneous pattern, despite its localization is often limited to one pole of the cell. During neuronal differentiation, positional information on the progenitor cells assumes an important role in acquiring polarization. The proper control of the cell orientation ensures a fine balancing between symmetric (giving rise to two progenitor sister cells) versus asymmetric (giving rise to one progenitor cell and one newborn neuron) division. This process results in the polar organization of the neural tube with a lumen indicating the basal part of the polarized neuronal progenitor cell; in the iPSC model the cells are organized in the ‘neural rosette’ and interestingly, PCDH19 is located at the center of the rosette, with other well-known markers of the lumen (N-cadherin and ZO-1). These data suggest that PCDH19 has a role in instructing the apico-basal polarity of the progenitor cells, thus regulating the development of a properly organized human brain.