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Fetal Neural Tube Stem Cells from Pax3 Mutant Mice Proliferate, Differentiate, and Form Synaptic Connections When Stimulated with Folic Acid
- Source :
- Stem Cells and Development. 21:321-330
- Publication Year :
- 2012
- Publisher :
- Mary Ann Liebert Inc, 2012.
-
Abstract
- Although maternal intake of folic acid (FA) prevents neural tube defects in 70% of the population, the exact mechanism of prevention has not been elucidated. We hypothesized that FA affects neural stem cell (NSC) proliferation and differentiation. This hypothesis was examined in a folate-responsive spina bifida mouse model, Splotch (Sp(-/-)), which has a homozygous loss-of-function mutation in the Pax3 gene. Neurospheres were generated with NSCs from the lower lumbar neural tube of E10.5 wild-type (WT) and Sp(-/-) embryos, in the presence and absence of FA. In the absence of FA, the number of neurospheres generated from Sp(-/-) embryos compared with WT was minimal (P0.05). Addition of FA to Sp(-/-) cultures increased the expression of a Pax3 downstream target, fgfr4, and rescued NSC proliferative potential, as demonstrated by a significant increase in neurosphere formation (P0.01). To ascertain if FA affected cell differentiation, FA-stimulated Sp(-/-) neurospheres were allowed to differentiate in the continued presence or absence of FA. Neurospheres from both conditions expressed multi-potent stem cell characteristics and the same differentiation potential as WT. Further, multiple neurospheres from both WT and FA-stimulated Sp(-/-) cell cultures formed extensive synaptic connections. On the whole, FA-mediated rescue of neural tube defects in Sp(-/-) embryos promotes NSC proliferation at an early embryonic stage. FA-stimulated Sp(-/-) neurospheres differentiate and form synaptic connections, comparable to WT.
- Subjects :
- Neural Tube
Cellular differentiation
Population
Biology
Gene Knockout Techniques
Mice
Fetus
Folic Acid
Neural Stem Cells
Neurosphere
medicine
Animals
Paired Box Transcription Factors
Receptor, Fibroblast Growth Factor, Type 4
education
PAX3 Transcription Factor
Spinal Dysraphism
Cell Proliferation
Mice, Knockout
Neurons
Genetics
education.field_of_study
Fetal Stem Cells
Homozygote
Neural tube
Gene Expression Regulation, Developmental
Cell Differentiation
Embryo
Cell Biology
Hematology
Embryo, Mammalian
Molecular biology
Neural stem cell
Disease Models, Animal
medicine.anatomical_structure
Synapses
Stem cell
Signal Transduction
Developmental Biology
Subjects
Details
- ISSN :
- 15578534 and 15473287
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Stem Cells and Development
- Accession number :
- edsair.doi.dedup.....873374fd6dd4b7fb5e61243c85f2cbe4