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Updated: Jul 2, 2026

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Published on: February 28, 2021
Broad mesodermal and endodermal deletion of Nodal at postgastrulation stages results solely in left/right axial
Amit Kumar1, Margaret Lualdi, Mark Lewandoski
1Laboratory of Protein Dynamics and Signaling, National Cancer Institute, NCI-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
Abstract:
Nodal signaling is a critical regulator of multiple aspects of early vertebrate development including asymmetry along the left/right (LR) axis. To study Nodal function occurring specifically in the postgastrulation embryo, we have used Cre/loxP based conditional mutagenesis. A floxed allele of Nodal was generated and shown to have wild-type function. This allele was then used in conjunction with the T-Cre line, which expresses Cre recombinase broadly in the mesodermal and definitive endodermal lineages posterior to the cranial region. T-Cre activity leads to complete deletion of Nodal before its normal transient expression in the early somite stage lateral plate mesoderm, thereby causing severe LR developmental defects. No other abnormalities were found, suggesting that Nodal signaling has no additional essential functions in developmental patterning within the extensive mesodermal and endodermal domains marked by T-Cre activity.
Insights
Nodal signaling is essential for left/right (LR) axis development in vertebrates. Conditional mutagenesis revealed Nodal
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Nodal signaling is crucial for vertebrate embryonic development, particularly left/right (LR) axis formation.
- Understanding Nodal's specific roles post-gastrulation requires precise genetic tools.
Purpose of the Study:
- To investigate the function of Nodal signaling specifically in the post-gastrulation embryo.
- To determine if Nodal has essential roles in mesodermal and endodermal patterning beyond LR axis development.
Main Methods:
- Generation of a floxed Nodal allele with wild-type function.
- Utilized the T-Cre conditional mutagenesis system to delete Nodal in mesodermal and endodermal lineages.
- Analysis of embryonic development following targeted Nodal deletion.
Main Results:
- Complete deletion of Nodal in the T-Cre expression domain abrogated normal transient expression in the lateral plate mesoderm.
- Severe left/right developmental defects were observed in mutant embryos.
- No other developmental abnormalities were detected in the affected tissues.
Conclusions:
- Nodal signaling is indispensable for establishing left/right asymmetry in vertebrate development.
- Nodal signaling does not appear to have essential functions in the broader patterning of mesodermal and endodermal tissues during post-gastrulation development.
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