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Updated: Jan 19, 2026
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Transgenic Analyses in Drosophila Reveal That mCORL1 Is Functionally Distinct from mCORL2 and dCORL
Michael J Stinchfield1, Keiji Miyazawa2, Stuart J Newfeld3
1School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501 and.
Abstract:
Uncovering how new members of multigene families acquire new functions is an important topic in evolutionary and developmental genetics. CORL proteins (SKOR in mice, Fussel in humans and fussel in Flybase) are a family of CNS specific proteins related to mammalian Sno/Ski oncogenes. Drosophila CORL (dCORL) participates in TGF-β and insulin signaling during development and in adult homeostasis but roles for the two mouse CORL proteins (mCORL) are essentially unknown. A series of studies were conducted to test the hypothesis based on previous results that mCORL1 is more similar to dCORL than mCORL2. Neither an updated alignment nor ectopic expression in adult wings were able to distinguish mCORL1 or mCORL2 from dCORL. Transgene experiments employing a dCORL endogenous function in mushroom body neurons showed that mCORL1 is distinct from mCORL2 and dCORL. mCORL1 and mCORL2 are also distinct in biochemical assays of Smad-binding and BMP signaling. Taken together, the data suggests testable new hypotheses for mCORL2 function in mammalian TGF-β and insulin signaling based on known roles for dCORL. Overall, the study reiterates the value of transgenic methods in Drosophila to provide new information on multigene family evolution and the function of family members in other species.
Insights
Mouse CORL proteins (mCORL) function differently than Drosophila CORL (dCORL). Transgenic studies in flies reveal distinct roles for mCORL1 and mCORL2, suggesting new hypotheses for their mammalian signaling functions.
Area of Science:
- Evolutionary genetics
- Developmental genetics
- Molecular biology
Background:
- CORL proteins are CNS-specific and related to Sno/Ski oncogenes.
- Drosophila CORL (dCORL) is involved in TGF-β and insulin signaling.
- Roles of mouse CORL proteins (mCORL1, mCORL2) are largely unknown.
Purpose of the Study:
- To test if mCORL1 is more similar to dCORL than mCORL2.
- To investigate the distinct functions of mCORL1 and mCORL2.
- To explore the evolutionary divergence of CORL family members.
Main Methods:
- Sequence alignment and ectopic expression in adult wings.
- Transgenic experiments using dCORL endogenous function in Drosophila mushroom body neurons.
- Biochemical assays for Smad-binding and BMP signaling.
Main Results:
- Neither sequence alignment nor ectopic expression distinguished mCORL1/mCORL2 from dCORL.
- Transgene experiments revealed mCORL1 is distinct from mCORL2 and dCORL.
- Biochemical assays showed mCORL1 and mCORL2 differ in Smad-binding and BMP signaling.
Conclusions:
- mCORL1 and mCORL2 have distinct functions, differing from dCORL.
- Data supports new hypotheses for mCORL2 function in mammalian TGF-β and insulin signaling.
- Drosophila transgenic methods are valuable for studying multigene family evolution and function across species.
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