Monoamine oxidase A expression is vital for embryonic brain development by modulating developmental apoptosis

Wang, C.C., Borchert, A., Ugun-Klusek, A. ORCID: 0000-0002-0199-0275, Tang, L.Y., Lui, W.T., Chu, C.Y., Billett, E. ORCID: 0000-0001-8245-6519, Kuhn, H. and Ufer, C., 2011. Monoamine oxidase A expression is vital for embryonic brain development by modulating developmental apoptosis. The Journal of Biological Chemistry, 286 (32). ISSN 0021-9258

[img]
Preview
Text
213058_8405 Billett Publisher PID213058.pdf

Download (9MB) | Preview

Abstract

Monoamine oxidases (MAO-A, MAO-B) metabolize biogenic amines and have been implicated in neuronal apoptosis. Although apoptosis is an important process in embryo development, the role of MAO isoenzymes has not been investigated in detail. We found that expression of MAO-A and MAO-B can be detected early on during embryo development. Expression levels remained constant until around midgestation but then dropped to almost undetectable levels toward birth. Similar expression kinetics were observed in the brain. Isoform-specific expression silencing of MAO-A mediated by siRNA during in vitro embryogenesis induced developmental defects, as indicated by a reduction of the crown rump length and impaired cerebral development. These alterations were paralleled by elevated serotonin levels. Similar abnormalities were observed when embryos were cultured in the presence of the MAO-A inhibitor clorgyline or when the transcriptional inhibitor of MAO-A expression Rl was overexpressed. In contrast, no such alterations were detected when expression of MAO-B was knocked down. To explore the underlying mechanisms for the developmental abnormalities in MAO-A knockdown embryos, we quantified the degree of developmental apoptosis in the developing brain. MAO-A knockdown reduced the number of apoptotic cells in the neuroepithelium, which coincided with impaired activation of caspases 3 and 9. Moreover, we observed reduced cyclin Dl levels as an indicator of impaired cell proliferation in MAO-A knockdown embryos. This data highlights MAO-A as a vital regulator of embryonic brain development.

Item Type: Journal article
Publication Title: The Journal of Biological Chemistry
Creators: Wang, C.C., Borchert, A., Ugun-Klusek, A., Tang, L.Y., Lui, W.T., Chu, C.Y., Billett, E., Kuhn, H. and Ufer, C.
Publisher: The American Society for Biochemistry and Molecular Biology, Inc.
Place of Publication: Rockville, Maryland, USA
Date: 2011
Volume: 286
Number: 32
ISSN: 0021-9258
Identifiers:
NumberType
10.1074/jbc.M111.241422DOI
Rights: © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Divisions: Schools > School of Science and Technology
Depositing User: EPrints Services
Date Added: 09 Oct 2015 11:13
Last Modified: 09 Jun 2017 13:53
URI: http://irep.ntu.ac.uk/id/eprint/24607

Actions (login required)

Edit View Edit View

Views

Views per month over past year

Downloads

Downloads per month over past year