Expansion of the lateral ventricles and ependymal deficits underlie the hydrocephalus evident in mice lacking the transcription factor NFIX

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dc.contributor.authorVidovic, D.
dc.contributor.authorHarris, L.
dc.contributor.authorHarvey, T.J.
dc.contributor.authorEvelyn Heng, Y.H.
dc.contributor.authorSmith, A.G.
dc.contributor.authorOsinski, J.
dc.contributor.authorHughes, J.
dc.contributor.authorThomas, P.
dc.contributor.authorGronostajski, R.M.
dc.contributor.authorBailey, T.L.
dc.contributor.authorPiper, M.
dc.date.issued2015
dc.description.abstractNuclear factor one X (NFIX) has been shown to play a pivotal role during the development of many regions of the brain, including the neocortex, the hippocampus and the cerebellum. Mechanistically, NFIX has been shown to promote neural stem cell differentiation through the activation of astrocyte-specific genes and via the repression of genes central to progenitor cell self-renewal. Interestingly, mice lacking Nfix also exhibit other phenotypes with respect to development of the central nervous system, and whose underlying causes have yet to be determined. Here we examine one of the phenotypes displayed by Nfix(-/-) mice, namely hydrocephalus. Through the examination of embryonic and postnatal Nfix(-/-) mice we reveal that hydrocephalus is first seen at around postnatal day (P) 10 in mice lacking Nfix, and is fully penetrant by P20. Furthermore, we examined the subcommissural organ (SCO), the Sylvian aqueduct and the ependymal layer of the lateral ventricles, regions that when malformed and functionally perturbed have previously been implicated in the development of hydrocephalus. SOX3 is a factor known to regulate SCO development. Although we revealed that NFIX could repress Sox3-promoter-driven transcriptional activity in vitro, SOX3 expression within the SCO was normal within Nfix(-/-) mice, and Nfix mutant mice showed no abnormalities in the structure or function of the SCO. Moreover, these mutant mice exhibited no overt blockage of the Sylvian aqueduct. However, the ependymal layer of the lateral ventricles was frequently absent in Nfix(-/-) mice, suggesting that this phenotype may underlie the development of hydrocephalus within these knockout mice.
dc.description.statementofresponsibilityDiana Vidovic, Lachlan Harris, Tracey J.Harvey, Yee Hsieh Evelyn Heng, Aaron G.Smith ... Paul Thomas ... et al.
dc.identifier.citationBrain Research, 2015; 1616:71-87
dc.identifier.doi10.1016/j.brainres.2015.04.057
dc.identifier.issn0006-8993
dc.identifier.issn1872-6240
dc.identifier.urihttp://hdl.handle.net/2440/123572
dc.language.isoen
dc.publisherElsevier
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1003462
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1057751
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1022308
dc.relation.granthttp://purl.org/au-research/grants/arc/FT120100170
dc.rights© 2015 Elsevier B.V. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.brainres.2015.04.057
dc.subjectNuclear factor one X; hydrocephalus; subcommissural organ; Reissner's fibre; transcription factor
dc.titleExpansion of the lateral ventricles and ependymal deficits underlie the hydrocephalus evident in mice lacking the transcription factor NFIX
dc.typeJournal article
pubs.publication-statusPublished

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