Elsevier

Developmental Biology

Volume 340, Issue 1, 1 April 2010, Pages 41-53
Developmental Biology

A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice

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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

Pericentrin
Interneuron migration
Brain development
Seckel syndrome
Microcephalic osteodysplastic primordial dwarfism (MOPD)
Schizophrenia
Rostral migratory stream (RMS)
Olfactory bulb

Cited by (0)

1

Present address: Department of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.

2

Present address: Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.