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A critical role of noggin in developing folate-nonresponsive NTD in Fkbp8 -/- embryos
- Source :
- Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery. 30(8)
- Publication Year :
- 2014
-
Abstract
- 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.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.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.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.
- Subjects :
- medicine.medical_specialty
Jumonji Domain-Containing Histone Demethylases
OLIG2
Tacrolimus Binding Proteins
Mice
Folic Acid
Neural Stem Cells
Pregnancy
Internal medicine
medicine
Animals
Humans
Folate intake
Neural Tube Defects
Noggin
Cell Proliferation
Homeodomain Proteins
Mice, Knockout
Neural tube defect
business.industry
Neural tube
Gene Expression Regulation, Developmental
Embryo
General Medicine
medicine.disease
Embryo, Mammalian
Neural stem cell
Mice, Inbred C57BL
Disease Models, Animal
medicine.anatomical_structure
Endocrinology
Pediatrics, Perinatology and Child Health
Female
Neurology (clinical)
business
Carrier Proteins
Subjects
Details
- ISSN :
- 14330350
- Volume :
- 30
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
- Accession number :
- edsair.doi.dedup.....d19d9ec17928577fdb6b707d9cac4622