Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.
Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD.
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.
Naoyuki
N
Matsumoto
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.
Yoshio
Y
Hoshiba
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.|Medical Research Training Program, School of Medicine, Kanazawa University.
Kazuya
K
Morita
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.|Medical Research Training Program, School of Medicine, Kanazawa University.
Natsu
N
Uda
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.|Medical Research Training Program, School of Medicine, Kanazawa University.
Miwako
M
Hirota
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.|Medical Research Training Program, School of Medicine, Kanazawa University.
Maki
M
Minamikawa
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.
Haruka
H
Ebisu
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.
Yohei
Y
Shinmyo
Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University.|Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan.
Hiroshi
H
Kawasaki
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D018274:Electroporation; D063928:Ependymoglial Cells / Q000378:metabolism; D005289:Ferrets / Q000235:genetics / Q000502:physiology; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D059330:GABAergic Neurons / Q000378:metabolism; D006801:Humans; D051379:Mice; D054091:Periventricular Nodular Heterotopia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D013796:Thanatophoric Dysplasia / Q000150:complications / Q000235:genetics / Q000503:physiopathology*
D051524:Fibroblast Growth Factor 8