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Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation
C M Jones1, M R Kuehn, B L Hogan
1Department of Cell Biology, Vanderbilt University Medical School, Nashville, TN 37232-2175, USA.
Abstract:
Mouse embryos homozygous for a null mutation in nodal arrest development at early gastrulation and contain little or no embryonic mesoderm. Here, two Xenopus nodal-related genes (Xnr-1 and Xnr-2) are identified and shown to be expressed transiently during embryogenesis, first within the vegetal region of late blastulae and later in the marginal zone during gastrulation, with enrichment in the dorsal lip. Xnrs and mouse nodal function as dose-dependent dorsoanterior and ventral mesoderm inducers in whole embryos and explanted animal caps. Using a plasmid vector to produce Xnr proteins during gastrulation, we show that, in contrast to activin and other TGF beta-like molecules, Xnr-1 and Xnr-2 can dorsalize ventral marginal zone explants and induce muscle differentiation. Xnr signalling also rescues a complete embryonic axis in UV-ventralized embryos. The patterns of Xnr expression, the activities of the proteins and the phenotype of mouse nodal mutants, all argue strongly that a signaling pathway involving nodal, or nodal-related peptides, is an essential conserved element in mesoderm differentiation associated with vertebrate gastrulation and axial patterning.
Insights
Xenopus nodal-related (Xnr) genes are crucial for mesoderm development and axial patterning in vertebrates. Their signaling pathway is essential for embryonic mesoderm formation and dorsal-ventral patterning during gastrulation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Mouse nodal mutations cause developmental arrest at gastrulation with absent embryonic mesoderm.
- Nodal signaling is implicated in mesoderm formation and axial patterning.
- Understanding conserved signaling pathways is key to deciphering vertebrate embryogenesis.
Purpose of the Study:
- Identify and characterize Xenopus nodal-related (Xnr) genes.
- Investigate the role of Xnrs in mesoderm induction and axial patterning.
- Compare Xnr function with other TGF-beta superfamily members.
Main Methods:
- Gene identification and expression analysis in Xenopus embryos.
- Functional studies using plasmid vectors to express Xnr proteins.
- Mesoderm induction assays with whole embryos and explanted animal caps.
- Rescue experiments in UV-ventralized embryos.
Main Results:
- Two Xenopus nodal-related genes, Xnr-1 and Xnr-2, were identified.
- Xnrs are transiently expressed in vegetal regions and marginal zones during gastrulation.
- Xnrs induce dorsal and ventral mesoderm in a dose-dependent manner.
- Xnr-1 and Xnr-2 dorsalize ventral explants, induce muscle differentiation, and rescue embryonic axes.
Conclusions:
- A conserved signaling pathway involving nodal-related peptides is essential for mesoderm differentiation and axial patterning in vertebrates.
- Xnr signaling plays a critical role in gastrulation and establishing the embryonic axis.
- Xnrs represent a conserved mechanism for mesoderm induction and patterning across vertebrate species.