Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis

Stegeman, Shane, Jolly, Lachlan A., Premarathne, Susitha, Gecz, Jozef, Richards, Linda J., Mackay-Sim, Alan and Wood, Stephen A.. (2013) Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis. PLoS ONE, 8 7: e68287.1-e68287.11. doi:10.1371/journal.pone.0068287

Author Stegeman, Shane
Jolly, Lachlan A.
Premarathne, Susitha
Gecz, Jozef
Richards, Linda J.
Mackay-Sim, Alan
Wood, Stephen A..
Title Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFβ-mediated axonogenesis
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0068287
Open Access Status DOI
Volume 8
Issue 7
Start page e68287.1
End page e68287.11
Total pages 12
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted 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-b 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-b signaling extends to neurons.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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Created: Thu, 25 Jul 2013, 14:22:36 EST by Debra McMurtrie on behalf of Queensland Brain Institute