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Type: Journal article
Title: Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice
Author: Lee, K.
Tan, J.
Morris, M.
Rizzoti, K.
Hughes, J.
Cheah, P.
Felquer, F.
Liu, X.
Piltz, S.
Lovell-Badge, R.
Thomas, P.
Citation: PLoS One, 2012; 7(1):1-12
Publisher: Public Library of Science
Issue Date: 2012
ISSN: 1932-6203
Editor: Schmidt, J.V.
Statement of
Kristie Lee, Jacqueline Tan, Michael B. Morris, Karine Rizzoti, James Hughes, Pike See Cheah, Fernando Felquer, Xuan Liu, Sandra Piltz, Robin Lovell-Badge and Paul Q. Thomas
Abstract: 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.
Keywords: Animals
Mice, Inbred C57BL
Mice, Inbred CBA
Midline Thalamic Nuclei
Subcommissural Organ
Abnormalities, Multiple
Green Fluorescent Proteins
Gene Dosage
Cell Differentiation
Embryo, Mammalian
Mice, Transgenic
SOXB1 Transcription Factors
Rights: Copyright: © 2012 Lee 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.
DOI: 10.1371/journal.pone.0029041
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Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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