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Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry inXenopus
- Source :
- Development. 138:475-485
- Publication Year :
- 2011
- Publisher :
- The Company of Biologists, 2011.
-
Abstract
- The spatiotemporally dynamic distribution of instructive ligands within embryonic tissue, and their feedback antagonists, including inherent stabilities and rates of clearance, are affected by interactions with cell surfaces or extracellular matrix (ECM). Nodal (here, Xnr1 or Nodal1 in Xenopus) and Lefty interact in a cross-regulatory relationship in mesendoderm induction, and are the conserved instructors of left-right (LR) asymmetry in early somitogenesis stage embryos. By expressing Xnr1 and Lefty proproteins that produce mature functional epitope-tagged ligands in vivo, we found that ECM is a principal surface of Nodal and Lefty accumulation. We detected Lefty moving faster than Nodal, with evidence that intact sulfated proteoglycans in the ECM facilitate the remarkable long distance movement of Nodal. We propose that Nodal autoregulation substantially aided by rapid ligand transport underlies the anteriorward shift of Nodal expression in the left LPM (lateral plate mesoderm), and speculate that the higher levels of chondroitin-sulfate proteoglycan (CSPG) in more mature anterior regions provide directional transport cues. Immunodetection and biochemical analysis showed transfer of Lefty from left LPM to right LPM, providing direct evidence that left-side-derived Lefty is a significant influence in ensuring the continued suppression of right-sided expression of Nodal, maintaining unilateral expression of this conserved determinant of asymmetry.
- Subjects :
- Mesoderm
Embryo, Nonmammalian
Nodal Protein
Left-Right Determination Factors
Xenopus
Blotting, Western
Fluorescent Antibody Technique
Nodal signaling
Xenopus Proteins
Somitogenesis
medicine
Animals
Molecular Biology
Body Patterning
Genetics
biology
Lateral plate mesoderm
Gene Expression Regulation, Developmental
Lefty
biology.organism_classification
Extracellular Matrix
Cell biology
medicine.anatomical_structure
Proteoglycans
NODAL
Research Article
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....5bacc89094c545eb422a2e1ff4fa0f9a
- Full Text :
- https://doi.org/10.1242/dev.056010