Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/79636
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Type: Journal article
Title: Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis
Other Titles: Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta-mediated axonogenesis
Author: Stegeman, S.
Jolly, L.
Premarathne, S.
Gecz, J.
Richards, L.
Mackay-Sim, A.
Wood, S.
Citation: PLoS One, 2013; 8(7):1-12
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Shane Stegeman, Lachlan A. Jolly, Susitha Premarathne, Jozef Gecz, Linda J. Richards, Alan Mackay-Sim and Stephen A. Wood
Abstract: The deubiquitylating enzyme Usp9x is highly expressed in the developing mouse brain, and increased Usp9x expression enhances the self-renewal of neural progenitors in vitro. USP9X is a candidate gene for human neurodevelopmental disorders, including lissencephaly, epilepsy and X-linked intellectual disability. To determine if Usp9x is critical to mammalian brain development we conditionally deleted the gene from neural progenitors, and their subsequent progeny. Mating Usp9xloxP/loxP mice with mice expressing Cre recombinase from the Nestin promoter deleted Usp9x throughout the entire brain, and resulted in early postnatal lethality. Although the overall brain architecture was intact, loss of Usp9x disrupted the cellular organization of the ventricular and sub-ventricular zones, and cortical plate. Usp9x absence also led to dramatic reductions in axonal length, in vivo and in vitro, which could in part be explained by a failure in Tgf-β signaling. Deletion of Usp9x from the dorsal telencephalon only, by mating with Emx1-cre mice, was compatible with survival to adulthood but resulted in reduction or loss of the corpus callosum, a dramatic decrease in hippocampal size, and disorganization of the hippocampal CA3 region. This latter phenotypic aspect resembled that observed in Doublecortin knock-out mice, which is an Usp9x interacting protein. This study establishes that Usp9x is critical for several aspects of CNS development, and suggests that its regulation of Tgf-β signaling extends to neurons.
Keywords: Central Nervous System; Cerebellar Cortex; Hippocampus; Astrocytes; Neurons; Axons; Animals; Mice, Knockout; Mice; Endopeptidases; Transforming Growth Factor beta; Organ Size; Signal Transduction; Gene Deletion; Genes, Lethal; Female; Male; Neurogenesis
Description: Extent: 12 p.
Rights: Copyright: © 2013 Stegeman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020130347
DOI: 10.1371/journal.pone.0068287
Grant ID: http://purl.org/au-research/grants/nhmrc/1009248
http://purl.org/au-research/grants/nhmrc/628952
http://purl.org/au-research/grants/nhmrc/250340
Appears in Collections:Obstetrics and Gynaecology publications

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