@article{e3e3e383e19141c7a48ee8efe94f8d0e,
title = "A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice",
abstract = "Precise control of neuronal migration is essential for proper function of the brain. Taking a forward genetic screen, we isolated a mutant mouse with defects in interneuron migration. By genetic mapping, we identified a frame shift mutation in the pericentrin (Pcnt) gene. The Pcnt gene encodes a large centrosomal coiled-coil protein that has been implicated in schizophrenia. Recently, frame shift and premature termination mutations in the pericentrin (PCNT) gene were identified in individuals with Seckel syndrome and microcephalic osteodysplastic primordial dwarfism (MOPD II), both of which are characterized by greatly reduced body and brain sizes. The mouse Pcnt mutant shares features with the human syndromes in its overall growth retardation and reduced brain size. We found that dorsal lateral ganglionic eminence (dLGE)-derived olfactory bulb interneurons are severely affected and distributed abnormally in the rostral forebrain in the mutant. Furthermore, mutant interneurons exhibit abnormal migration behavior and RNA interference knockdown of Pcnt impairs cell migration along the rostal migratory stream (RMS) into the olfactory bulb. These findings indicate that pericentrin is required for proper migration of olfactory bulb interneurons and provide a developmental basis for association of pericentrin function with interneuron defects in human schizophrenia.",
keywords = "Brain development, Interneuron migration, Microcephalic osteodysplastic primordial dwarfism (MOPD), Olfactory bulb, Pericentrin, Rostral migratory stream (RMS), Schizophrenia, Seckel syndrome",
author = "Setsu Endoh-Yamagami and Karkar, {Kameel M.} and May, {Scott R.} and Inma Cobos and Thwin, {Myo T.} and Long, {Jason E.} and Ashique, {Amir M.} and Konstantinos Zarbalis and Rubenstein, {John L.R.} and Peterson, {Andrew S.}",
note = "Funding Information: We thank F. Polleux and D. Bortone for sharing plasmids, techniques of electroporation and slice culture, and a method for cell migration quantification. We also thank Y. Choe for his technical help in Pcnt immunoblot analysis. We thank D. Gray and D. Davis for the miRNA vector plasmid and advice, J. Starks, M. Nee and R. Asuncion and C. Byers for animal husbandry, I. Fodor, M. Friesenhahn, A. Hartford, W. Forrest and N. Lewin-Koh for advice in statistics, and M. Solloway, D. Slaga and A. Minn for careful reading of this manuscript. The Pax6 antibody developed by A. Kawakami was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. This work was initiated at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco, where support was provided by grants from the National Institutes of Health to A.S.P. It was also supported by postdoctoral fellowship from the Uehara Memorial Foundation to S.E-Y. and NARSAD Young Investigator Award to K.M.K. We thank the Gallo center for use of line 239 mice, and Y. Yanagawa and Gunma University for the transgenic GAD67-GFP line. ",
year = "2010",
month = apr,
day = "1",
doi = "10.1016/j.ydbio.2010.01.017",
language = "English (US)",
volume = "340",
pages = "41--53",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Elsevier Inc.",
number = "1",
}