title: 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.
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.
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Compagnucci
authors.affiliation: Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.affiliation: Central Research Institute for the Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan.
authors.forename: Norimichi
authors.initials: N
authors.lastname: Higuraschi
authors.affiliation: Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Trivisano
authors.affiliation: Division of Neurology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Specchio
authors.affiliation: Central Research Institute for the Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Unit of Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Terracciano
mesh_terms: D001921:Brain / Q000196:embryology / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation; D016764:Cell Polarity; D049109:Cell Proliferation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D054259:Neural Tube / Q000473:pathology; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000091363:Protocadherins; D013234:Stem Cells / Q000166:cytology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: Neuroscience Section; PCDH19; human iPSCs; iPSC-derived neurons; neural rosettes; neuronal polarity