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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Liu, Chen Goswami, Mousumi Talley, Julia Chesser-Martinez, Patricia L. Lou, Chih-Hong Sater, Amy K. |
| Description | Country affiliation: United States Author Affiliation: Liu C ( Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5001, USA.) |
| Abstract | FGFs and BMPs act in concert to regulate a wide range of processes in vertebrate development. In most cases, FGFs and BMPs have opposing effects, and specific developmental outcomes arise out of a balance between the two growth factors. We and others have previously demonstrated that signaling pathways activated by FGFs and BMPs interact via inhibitory crosstalk. Here we demonstrate a role for the BMP effector TGF-ß Activated Kinase 1 (TAK1) in the maintenance of Smad1 activity in Xenopus embryos, via the inhibition of erk MAPK. Up- or downregulation of TAK1 levels produces an inverse alteration in the amount of activated erk MAPK. The inhibition of erk MAPK by TAK1 is mediated by p38 and a corresponding decrease in phosphorylation of MEK. TAK1 morphant embryos show a decrease in the nuclear accumulation of Smad1. Conversely, reduction of erk MAPK activity via overexpression of MAP Kinase Phosphatase1 (MKP1) leads to an increase in nuclear Smad1. Both TAK1 morphant ectoderm and ectoderm treated with FGF show a decrease in the expression of several Smad1-inducible genes. Neural-specific gene expression is inhibited in isolated ectoderm coexpressing noggin and TAK1, suggesting that TAK1 is sufficient to inhibit neural specification. Introduction of TAK1 morpholino oligonucleotide expands the expression of organizer genes, disrupts formation of the boundary between organizer and non-organizer mesoderm, and increases the spatial range of MAPK activation in response to localized FGF. Our results indicate that inhibitory interactions between FGF and BMP4 effector pathways increase the robustness of BMP signaling via a feed-forward mechanism. |
| File Format | HTM / HTML |
| ISSN | 03014681 |
| Issue Number | 4 |
| Volume Number | 83 |
| e-ISSN | 14320436 |
| Journal | Differentiation |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Embryology Discipline Biology Bone Morphogenetic Protein 4 Metabolism Extracellular Signal-regulated Map Kinases Antagonists & Inhibitors Fibroblast Growth Factors Physiology Map Kinase Kinase Kinases Signal Transduction Smad1 Protein Xenopus Proteins Animals Down-regulation Immunohistochemistry In Situ Hybridization Real-time Polymerase Chain Reaction Xenopus Embryology Journal Article Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology Molecular Biology Cancer Research |
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