Related Experiment Video
Updated: Oct 1, 2026
Three and Four-Dimensional Visualization and Analysis Approaches to Study Vertebrate Axial Elongation and Segmentation
Published on: February 28, 2021
Hypomorphic Mesp allele distinguishes establishment of rostrocaudal polarity and segment border formation in
Aya Nomura-Kitabayashi1, Yu Takahashi, Satoshi Kitajima
1Cellular and Molecular Toxicology Division, National Institute of Health Sciences, 1-18-1 Kamiyohga, Setagaya-ku, Tokyo 158-8501, Japan.
Abstract:
A bHLH-type transcription factor, Mesp2, plays an essential role in somite segmentation in mice. Zebrafish mespb (mesp-b), a putative homologue of mouse Mesp2, is transiently expressed in the rostral presomitic mesoderm similarly to Mesp2. To determine whether zebrafish mespb is a functional homologue of mouse Mesp2, zebrafish mespb was introduced into the mouse Mesp2 locus by homologous recombination. Introduced mespb almost rescued the Mesp2 deficiency in the homozygous mespb knockin mouse, indicating that mespb is a functional homologue of mouse Mesp2. Segmented somites were clearly observed although the partial fusion of the vertebral columns still occurred. Interestingly, however, the nature and dosage of the mespb gene affected the rescue event. A mouse line, which has a hypomorphic Mesp2 allele generated by the introduction of neo-mespb, gave rise to an epithelial somite without normal rostrocaudal (RC) polarity. RC polarity was also lacking in the presomitic mesoderm. The defects in RC polarity were determined by the altered expressions of Uncx4.1 and Dll1 in the segmented somites and presomitic mesoderm, respectively. In contrast, the expression of EphA4 (Epha4), lunatic fringe or protocadherin, thought to be involved in segment border formation, was fairly normal in hypomorphic mutant embryos. These results suggest that the Mesp family of transcription factors is involved in both segment border formation and establishment of RC polarity through different genetic cascades.
Insights
Zebrafish mespb gene functionally complements mouse Mesp2, acting as a homologue. It is crucial for somite segmentation and rostrocaudal polarity establishment in mice, influencing gene expression cascades.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Mesp2, a bHLH transcription factor, is vital for mouse somite segmentation.
- Zebrafish mespb (mesp-b) exhibits similar expression patterns to mouse Mesp2 in the presomitic mesoderm.
Purpose of the Study:
- To investigate if zebrafish mespb is a functional homologue of mouse Mesp2.
- To elucidate the role of Mesp family transcription factors in somite segmentation and rostrocaudal polarity.
Main Methods:
- Homologous recombination was used to introduce the zebrafish mespb gene into the mouse Mesp2 locus.
- Analysis of somite segmentation, vertebral column formation, and gene expression (Uncx4.1, Dll1, EphA4) in genetically modified mice.
Main Results:
- Zebrafish mespb partially rescued Mesp2 deficiency in mice, confirming its functional homology.
- Hypomorphic alleles of mespb led to defects in somite epithelialization and loss of rostrocaudal polarity.
- Altered expression of Uncx4.1 and Dll1, but not EphA4, was observed in hypomorphic mutants, suggesting distinct genetic pathways.
Conclusions:
- Zebrafish mespb is a functional homologue of mouse Mesp2, essential for somite segmentation.
- Mesp family transcription factors regulate both segment border formation and rostrocaudal polarity through separate genetic cascades.
