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Zebrafish Meis functions to stabilize Pbx proteins and regulate hindbrain patterning
A J Waskiewicz1, H A Rikhof, R E Hernandez
1Howard Hughes Medical Institute, Division of Basic Sciences and Program in Developmental Biology, B2-152, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA.
Development (Cambridge, England)
|October 31, 2001
Summary
Meis protein partners with Pbx proteins to regulate zebrafish hindbrain segmentation. Meis also stabilizes Pbx protein levels, rescuing developmental defects in Pbx mutants.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Hox proteins control segmental identity, interacting with partners like Extradenticle (Exd) and Homothorax (Hth).
- Vertebrate homologs Pbx and Meis form complexes with Hox proteins, crucial for development.
- Pbx4/Lazarus (Lzr) is essential for zebrafish hindbrain segmentation and Hox gene regulation.
Purpose of the Study:
- To investigate the role of Meis in zebrafish hindbrain segmentation alongside Pbx.
- To elucidate the functional relationship between Meis and Pbx during development.
Main Methods:
- Expression of dominant-negative Meis in zebrafish embryos.
- Analysis of hindbrain segmentation phenotypes in Meis-manipulated embryos.
- Assessment of Lzr protein levels in response to Meis overexpression and mutations.
Main Results:
- Dominant-negative Meis expression phenocopies lzr mutations, indicating pathway involvement.
- Meis overexpression partially rescues the lzr mutant phenotype.
- Meis stabilizes Lzr protein levels, suggesting a post-transcriptional regulatory mechanism.
Conclusions:
- Meis functions as a DNA-binding partner of Pbx proteins in hindbrain segmentation.
- Meis acts as a post-transcriptional regulator, stabilizing Pbx protein levels.
- These dual roles highlight Meis's critical importance in zebrafish hindbrain development.