PUBLICATION
Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway
- Authors
- Alexandrova, E.M., and Thomsen, G.H.
- ID
- ZDB-PUB-110823-23
- Date
- 2006
- Source
- Developmental Biology 299(2): 398-410 (Journal)
- Registered Authors
- Keywords
- smurf1, smad1, BMP, ubiquitin ligase, neural tube, neural folding, neural patterning, signal transduction, embryo, xenopus laevis
- MeSH Terms
-
- Gastrula/metabolism*
- Nervous System/embryology*
- Nervous System/metabolism
- Signal Transduction
- Base Sequence
- Gene Expression Regulation, Developmental
- Smad1 Protein/physiology*
- Sequence Alignment
- Animals
- Xenopus laevis/embryology*
- Xenopus laevis/metabolism
- Bone Morphogenetic Proteins/physiology*
- Ubiquitin-Protein Ligases/genetics
- Ubiquitin-Protein Ligases/physiology*
- PubMed
- 16973150 Full text @ Dev. Biol.
Citation
Alexandrova, E.M., and Thomsen, G.H. (2006) Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway. Developmental Biology. 299(2):398-410.
Abstract
The ubiquitin ligase Smurf1 can target a handful of signaling proteins for ubiquitin-mediated proteasomal destruction or functional modification, including TGF-β receptors, Smads, transcription factors, RhoA and MEKK2. Smurf1 was initially implicated in BMP pathway regulation in embryonic development, but its potential role in vertebrate embryogenesis has yet to be clarified. Here we demonstrate that inhibition of Smurf1 in Xenopus laevis embryos with an antisense morpholino oligonucleotide or a dominant-negative protein disrupts early development, with the nervous system being the principal target. Smurf1 is enriched on the dorsal side of gastrula stage embryos, and blocking Smurf1 disturbs neural folding and neural, but not mesoderm differentiation, enhances BMP/Smad1 signaling, and elevates phospho-Smad1 levels in the dorsal ectoderm. We conclude that in Xenopus embryos, the BMP pathway is a major physiological target of Smurf1, and we propose that in normal development Smurf1 cooperates with secreted BMP antagonists to limit BMP signaling in dorsal ectoderm. Our data also reveal a novel role for Smurf1 and Smad1 in neural plate morphogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping