| First Author | Warner DR | Year | 2011 |
| Journal | Cell Biol Int | Volume | 35 |
| Issue | 12 | Pages | 1253-9 |
| PubMed ID | 21649587 | Mgi Jnum | J:222232 |
| Mgi Id | MGI:5644149 | Doi | 10.1042/CBI20110025 |
| Citation | Warner DR, et al. (2011) Altered signal transduction in Folr1-/- mouse embryo fibroblasts. Cell Biol Int 35(12):1253-9 |
| abstractText | Mice lacking the gene for Folr1 (folic acid receptor 1) have an NTD (neural tube defect) that is rescued by maternal folate supplementation. Primary cultures of MEFs (mouse embryonic fibroblasts) were established from these embryos and the effect on various signalling pathways examined. TGFbeta1 (transforming growth factor beta1) inhibited the proliferation of wild-type and Folr1-/- MEFs, and folate restriction, either in growth medium or through folate uptake, led to further inhibition of growth. This effect may be Smad-independent because reporter assays using the Smad-dependent reporter, p3TP-lux, revealed attenuation of TGFbeta1/Smad signalling in Folr1-/- MEFs. Signalling through the canonical Wnt pathway, measured by Wnt-3a stimulated expression of the target gene, Axin2, demonstrated increased activity in Folr1-/- MEFs. Only minor changes in the expression of a panel of TGFbeta (transforming growth factor beta) and Wnt pathway-associated genes were revealed when Folr1-/- MEFs were compared with wild-type cells. These results demonstrate that under conditions of reduced folate (Folr-/-) signalling, pathways crucial for proper development of the neural tube are significantly altered. |
