Hydrocephalus and abnormal subcommissural organ in mice lacking presenilin-1 in Wnt1 cell lineages

Nakajima, Miki; Matsuda, Keiko; Miyauchi, Naho; Fukunaga, Yasuyoshi; Watanabe, Sono; Okuyama, Satoshi; Pérez, Juan; Fernández-Llébrez, Pedro; Shen, Jie; Furukawa, Yoshiko

doi:10.1016/j.brainres.2011.01.048

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…10). To investigate this further, we measured the dorsoventral length of the Sylvian aqueduct at three different levels on coronal sections of P15 wild-type and knockout brains, a measure that has previously been utilised as a proxy for aqueductal stenosis (Nakajima et al, 2011). Again, we saw no significant alterations in this measure of aqueductal morphology between wild-type and knockout brains (Fig.…”

Section: 5mentioning

confidence: 91%

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

et al. 2015

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Nuclear 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.

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Section: 5mentioning

confidence: 91%

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

et al. 2015

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“…Sspo is also the primary component of Reissner's fiber (RF), a proteinaceous filament that originates from the SCO and threads through the central canal of the spinal cord in most vertebrate species [16,29,32]. RF has been reported to function in embryonic axis extension [19], maintaining the opening of the Sylvian aqueduct between the third and fourth ventricles [34], as well as in promoting CSF homeostasis through the clearance of monoamines [13,14]. Although defects in CSF flow and homeostasis have been linked to AIS pathogenesis [8,9], the roles for Sspo, the SCO, and RF in spine development have not yet been investigated.…”

Section: Reportmentioning

confidence: 99%

SCO-Spondin Defects and Neuroinflammation Are Conserved Mechanisms Driving Spinal Deformity across Genetic Models of Idiopathic Scoliosis

et al. 2020

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“…The SCO is a small secretary organ derived from prosomere 1, and is located in the dorsal midline of the third ventricle near the dorso-anterior opening of the Aq. Abnormal SCO development in mice with loss-of-function mutations or ectopic/overexpression of transgenes is also frequently associated with CH [10] , [12] , [13] , [14] , [15] , [16] .…”

Section: Introductionmentioning

confidence: 99%

“…Immunological blockage of RF generation results in stenosis of the Aq and subsequent hydrocephalus [17] , indicating that RF is critical for maintaining CSF flow through the Aq. Together, these studies point to a model in which RF generated by the SCO maintains patency of the Aq thereby preventing hydrocephalus [10] , [12] , [13] , [14] , [15] , [16] . However, the causal link between SCO dysfunction and CH has not been adequately resolved as some genetic mouse models of CH with SCO dysplasia also have ciliary and/or ChP pathology [8] , [10] , [12] or a lack of overt Aq stenosis [8] , [16] .…”

Section: Introductionmentioning

confidence: 99%

Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

et al. 2012

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Congenital hydrocephalus (CH) is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage) of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles) is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO) a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF), a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner.

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Hydrocephalus and abnormal subcommissural organ in mice lacking presenilin-1 in Wnt1 cell lineages

Cited by 8 publications

References 41 publications

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

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

SCO-Spondin Defects and Neuroinflammation Are Conserved Mechanisms Driving Spinal Deformity across Genetic Models of Idiopathic Scoliosis

Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

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