Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development Journal Article
| Authors: | Basson, M. A.; Echevarria, D.; Ahn, C. P.; Sudarov, A.; Joyner, A. L.; Mason, I. J.; Martinez, S.; Martin, G. R. |
| Article Title: | Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development |
| Abstract: | Prospective midbrain and cerebellum formation are coordinated by FGF ligands produced by the isthmic organizer. Previous studies have suggested that midbrain and cerebellum development require different levels of FGF signaling. However, little is known about the extent to which specific regions within these two parts of the brain differ in their requirement for FGF signaling during embryogenesis. Here, we have explored the effects of inhibiting FGF signaling within the embryonic mouse midbrain (mesencephalon) and cerebellum (rhombomere 1) by misexpressing sprouty2 (Spry2) from an early stage. We show that such Spry2 misexpression moderately reduces FGF signaling, and that this reduction causes cell death in the anterior mesencephalon, the region furthest from the source of FGF ligands. Interestingly, the remaining mesencephalon cells develop into anterior midbrain, indicating that a low level of FGF signaling is sufficient to promote only anterior midbrain development. Spry2 misexpression also affects development of the vermis, the part of the cerebellum that spans the midline. We found that, whereas misexpression of Spry2 alone caused loss of the anterior vermis, reducing FGF signaling further, by decreasing Fgf8 gene dose, resulted in loss of the entire vermis. Our data suggest that cell death is not responsible for vermis loss, but rather that it fails to develop because reducing FGF signaling perturbs the balance between vermis and roof plate development in rhombomere 1. We suggest a molecular explanation for this phenomenon by providing evidence that FGF signaling functions to inhibit the BMP signaling that promotes roof plate development. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; nonhuman; protein function; mouse; animals; mice; cell death; cell viability; cerebellum; apoptosis; cell maturation; bone morphogenetic protein; embryo; embryo development; gene expression regulation, developmental; brain development; embryo, mammalian; midbrain; mesencephalon; fibroblast growth factor; fibroblast growth factors; embryonic development; sprouty protein; fibroblast growth factor 8; integrases; cerebellum vermis; fgf; roof plate; sprouty; vermis; sprouty 2 protein; neuromere |
| Journal Title: | Development |
| Volume: | 135 |
| Issue: | 5 |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Date Published: | 2008-03-01 |
| Start Page: | 889 |
| End Page: | 898 |
| Language: | English |
| DOI: | 10.1242/dev.011569 |
| PUBMED: | 18216176 |
| PROVIDER: | scopus |
| PMCID: | PMC2555978 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 31" - "Export Date: 17 November 2011" - "CODEN: DEVPE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work