Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49477
Title: SEARCH FOR NOVEL REGULATORS OF BRAIN CIRCULATION AND THEIR FUNCTIONAL ANALYSIS
Authors: SHEN HONGYUAN
Keywords: kcng4, kcnb1, silent Kv subunit, cell proliferation, brain ventricular zone, hydrocephalus
Issue Date: 25-Nov-2013
Source: SHEN HONGYUAN (2013-11-25). SEARCH FOR NOVEL REGULATORS OF BRAIN CIRCULATION AND THEIR FUNCTIONAL ANALYSIS. ScholarBank@NUS Repository.
Abstract: The brain ventricular system is a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. Due to its immediate contact with neural stem cells, it plays an essential role in regulating neuronal function. While the gross anatomy of ventricular system and CSF hydrodynamics are well documented, the molecular mechanisms underlying their development are poorly understood. In this study, a zebrafish forward genetic screen was carried out using Tol2 transposon-mediated gene-breaking insertional mutagenesis to identify novel molecular regulators of brain circulation. Among all the mutants generated, a kcng4b mutant, which lacks Kv6.4b silent subunit function, displayed developmental defects in embryonic brain ventricles, including neuroepithelial cells delamination and hydrocephalus. Functional analyses of the mutant provide in vivo evidence that the silent Kv6.4b subunits play an essential role in regulating embryonic brain lumen inflation by modulating neuroepithelial cell proliferation and maintaining neuroepithelium integrity, presumably through the formation of Kv2.1/Kv6.4b heterotetramers at the embryonic brain ventricular zone. These results provide a functional basis for the modulation of Kv2.1 by silent Kv6.4b subunits during vertebrate embryonic brain ventricle morphogenesis.
URI: http://scholarbank.nus.edu.sg/handle/10635/49477
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