Drosophila Ror is a nervous system-specific co-receptor for Wnt ligands

Area of Science:

• Molecular Biology
• Developmental Biology
• Neuroscience

Background:

• Wnt ligands are crucial secreted glycoproteins regulating cellular processes and tissue homeostasis.
• Wnt signaling involves receptor complexes, typically Frizzled proteins and co-receptors like Ror, PTK7, Ryk, and MUSK.
• While Ror-2 and PTK7 regulate planar cell polarity (PCP) in vertebrates, their role in Drosophila, particularly PTK7 orthologs off-track (otk) and off-track2 (otk2), is unclear.

Purpose of the Study:

• To investigate the function and interactions of Drosophila Ror in the nervous system.
• To determine if Drosophila Ror plays a role in planar cell polarity (PCP).
• To identify the binding partners of Drosophila Ror.

Main Methods:

• Generated a null allele of Drosophila Ror.
• Analyzed Ror expression patterns in the nervous system.
• Performed genetic interaction studies with otk and otk2 mutations.
• Conducted binding assays with Wnt ligands and Frizzled proteins.

Main Results:

• Drosophila Ror is expressed in the nervous system, localizing to the plasma membrane of neurons.
• A null allele of Ror is viable and fertile, showing no PCP phenotypes.
• Ror genetically interacts with otk and otk2 mutations.
• Ror specifically binds to Wingless (Wg), Wnt4, Wnt5, Frizzled2 (Fz2), and Otk.

Conclusions:

• Drosophila Ror functions as a Wnt co-receptor in the nervous system.
• Ror's role in Drosophila does not appear to involve PCP, unlike its vertebrate counterparts.
• Ror's interactions with Wnts and Frizzled proteins highlight its significance in Wnt pathway regulation within the fly nervous system.