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A critical role of noggin in developing folate-nonresponsive NTD in Fkbp8 -/- embryos

Authors
 Takao Tsurubuchi,  ;  Elise V. Allender  ;  M. Rizwan Siddiqui  ;  Kyu-Won Shim  ;  Shunsuke Ichi  ;  Vanda Boshnjaku  ;  Barbara Mania-Farnell  ;  Guifa Xi  ;  Richard H. Finnell  ;  David G. McLone  ;  Tadanori Tomita  ;  C. S. Mayanil 
Citation
 CHILDS NERVOUS SYSTEM, Vol.30(8) : 1343-1353, 2014 
Journal Title
 CHILDS NERVOUS SYSTEM 
ISSN
 0256-7040 
Issue Date
2014
Abstract
PURPOSE: Maternal folate intake has reduced the incidence of human neural tube defects by 60-70 %. However, 30-40 % of cases remain nonresponsive to folate intake. The main purpose of this study was to understand the molecular mechanism of folate nonresponsiveness in a mouse model of neural tube defect. METHODS: We used a folate-nonresponsive Fkbp8 knockout mouse model to elucidate the molecular mechanism(s) of folate nonresponsiveness. Neurospheres were grown from neural stem cells isolated from the lumbar neural tube of E9.5 Fkbp8 (-/-) and wild-type embryos. Immunostaining was used to determine the protein levels of oligodendrocyte transcription factor 2 (Olig2), Nkx6.1, class III beta-tubulin (TuJ1), O4, glial fibrillary acidic protein (GFAP), histone H3 Lys27 trimethylation (H3K27me3), ubiquitously transcribed tetratricopeptide repeat (UTX), and Msx2, and quantitative real-time (RT)-PCR was used to determine the message levels of Olig2, Nkx6.1, Msx2, and noggin in neural stem cells differentiated in the presence and absence of folic acid. RESULTS: Fkbp8 (-/-)-derived neural stem cells showed (i) increased noggin expression; (ii) decreased Msx2 expression; (iii) premature differentiation--neurogenesis, oligodendrogenesis (Olig2 expression), and gliogenesis (GFAP expression); and (iv) increased UTX expression and decreased H3K27me3 polycomb modification. Exogenous folic acid did not reverse these markers. CONCLUSIONS: Folate nonresponsiveness could be attributed in part to increased noggin expression in Fkbp8 (-/-) embryos, resulting in decreased Msx2 expression. Folate treatment further increases Olig2 and noggin expression, thereby exacerbating ventralization.
Full Text
https://link.springer.com/article/10.1007%2Fs00381-014-2428-1
DOI
10.1007/s00381-014-2428-1
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Shim, Kyu Won(심규원) ORCID logo https://orcid.org/0000-0002-9441-7354
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/158615
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