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Drosophila engrailed can substitute for mouse Engrailed1 function in mid-hindbrain, but not limb development
M C Hanks1, C A Loomis, E Harris
1Developmental Genetics Program and Howard Hughes Medical Institute, Skirball Institute of Biomolecular Medicine and Departments of Cell Biology and Physiology and Neuroscience, NYU Medical Center, New York, NY 10016, USA.
Development (Cambridge, England)
|October 21, 1998
Summary
The Engrailed-1 gene (En1) in mice and the engrailed gene (en) in fruit flies share conserved functions in brain development. However, En1 has evolved unique roles in limb development not replicated by the fly gene.
Area of Science:
- Developmental Biology
- Evolutionary Biology
- Genetics
Background:
- The Engrailed-1 gene (En1) is crucial for mammalian midbrain, cerebellum, and limb development.
- The Drosophila engrailed (en) gene regulates segmentation and other patterning processes.
- Understanding the evolutionary conservation of Engrailed protein function is key to diverse developmental roles.
Purpose of the Study:
- To investigate the evolutionary conservation of biochemical properties between mouse En1 and Drosophila en.
- To determine if Drosophila en can rescue En1-deficient mouse phenotypes.
Main Methods:
- Replaced mouse En1 coding sequences with Drosophila en sequences in mice.
- Assessed rescue of brain, skeletal, and limb patterning defects in En1 mutant mice expressing Drosophila en.
Main Results:
- Drosophila en expression rescued lethal brain defects and most skeletal abnormalities in En1 mutant mice.
- Drosophila en failed to rescue embryonic limb dorsal/ventral patterning defects or Wnt7a repression.
- Neither En2 nor Drosophila en rescued postnatal limb abnormalities in surviving En1 null mutants.
Conclusions:
- Biochemical activity for brain development is conserved across phyla in Engrailed proteins.
- Vertebrate En proteins have acquired unique functions in embryonic and postnatal limb development.
- Only En1 possesses the necessary function for postnatal limb development rescue.