Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science
2012
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| Online Access: | http://psasir.upm.edu.my/id/eprint/24707/1/24707.PDF |
| _version_ | 1825925626825015296 |
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| author | Lee, Kristie Tan, Jacqueline Morris, Michael B. Rizzoti, Karine Hughes, James Cheah, Pike See Felquer, Fernando Xuan, Liu Piltz, Sandra Lovell-Badge, Robin Thomas, Paul Q. |
| author_facet | Lee, Kristie Tan, Jacqueline Morris, Michael B. Rizzoti, Karine Hughes, James Cheah, Pike See Felquer, Fernando Xuan, Liu Piltz, Sandra Lovell-Badge, Robin Thomas, Paul Q. |
| author_sort | Lee, Kristie |
| collection | UPM |
| description | 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. |
| first_indexed | 2024-03-06T08:00:39Z |
| format | Article |
| id | upm.eprints-24707 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T08:00:39Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | upm.eprints-247072019-10-01T04:31:38Z http://psasir.upm.edu.my/id/eprint/24707/ Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice Lee, Kristie Tan, Jacqueline Morris, Michael B. Rizzoti, Karine Hughes, James Cheah, Pike See Felquer, Fernando Xuan, Liu Piltz, Sandra Lovell-Badge, Robin Thomas, Paul Q. 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. Public Library of Science 2012-01-26 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/24707/1/24707.PDF Lee, Kristie and Tan, Jacqueline and Morris, Michael B. and Rizzoti, Karine and Hughes, James and Cheah, Pike See and Felquer, Fernando and Xuan, Liu and Piltz, Sandra and Lovell-Badge, Robin and Thomas, Paul Q. (2012) Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice. PLOS ONE, 7 (1). art. no. e29041. pp. 1-12. ISSN 1932-6203 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029041 10.1371/journal.pone.0029041 |
| spellingShingle | Lee, Kristie Tan, Jacqueline Morris, Michael B. Rizzoti, Karine Hughes, James Cheah, Pike See Felquer, Fernando Xuan, Liu Piltz, Sandra Lovell-Badge, Robin Thomas, Paul Q. Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice |
| title | Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice |
| title_full | Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice |
| title_fullStr | Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice |
| title_full_unstemmed | Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice |
| title_short | Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice |
| title_sort | congenital hydrocephalus and abnormal subcommissural organ development in sox3 transgenic mice |
| url | http://psasir.upm.edu.my/id/eprint/24707/1/24707.PDF |
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