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Isoform‐specific knockdown of monoamine oxidase expression retards murine embryogenesis via inhibition of developmental apoptosis
Author(s) -
Kuehn Hartmut,
Borchert Astrid,
Wang Chi Chui,
Ufer Christoph,
Billett Ellen
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.526.13
Subject(s) - gene knockdown , apoptosis , embryogenesis , microbiology and biotechnology , biology , gene isoform , programmed cell death , monoamine oxidase , embryo , enzyme , biochemistry , gene
Monoamine oxidases are key enzymes in metabolism of biogenic amines. Their role in the nervous systems is well established but their function in cerebral embryogenesis has not been well characterized. We explored expression of MAO during murine embryogenesis and found that MAO‐A and MAO‐B are expressed as early as E6.5. Expression levels remain constant until E13.5 but then dropped down to almost undetectable levels at birth. In brain similar expression kinetics were monitored. Pharmacological inhibition and siRNA‐mediated knockdown of MAO‐A expression induced severe developmental retardations and significant impairment of developmental brain scores. Such alterations were not observed when expression of MAO‐B was silenced. To explore the molecular basis for these effects we quantified the degree of apoptosis in siRNA treated embryos and found reduced numbers of apoptotic cells in epithelium of the neural tube. These alterations were paralleled by impaired activation of caspase 3 and augmented cyclin D1 expression. These data indicate that knockdown of MAO‐A impairs developmental apoptosis preventing activation of caspase‐3 leading to uncoordinated cell proliferation.