Genetic dissection of nodal function in patterning the mouse embryo.

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Transforming growth factor-like nodal signaling is known to be essential for mouse mesoderm development.
• Previous loss-of-function studies were limited by null mutations blocking gastrulation, hindering analysis of later developmental roles.

Purpose of the Study:

• To investigate the function of nodal signaling in mouse embryonic development beyond mesoderm formation.
• To overcome the limitations of null mutations by analyzing a hypomorphic nodal allele.

Main Methods:

• Generation and analysis of a hypomorphic nodal allele in mice.
• Phenotypic analysis of mouse embryos heterozygous for the hypomorphic allele and a null allele.
• Categorization of mutant phenotypes into distinct classes based on observed abnormalities.

Main Results:

• Mouse embryos with the hypomorphic allele exhibited gastrulation but developed abnormalities in three distinct phenotypic classes.
• Nodal signaling is required for establishing the anteroposterior axis.
• Nodal signaling regulates anterior and midline patterning, as well as left-right asymmetric development of organs like the heart, lungs, and stomach.

Conclusions:

• Nodal signaling plays critical roles in multiple mouse embryonic developmental processes beyond mesoderm formation.
• The hypomorphic allele provides a valuable tool for dissecting nodal function in development.
• Nodal signaling is essential for establishing body axes and asymmetric organ development.