Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis

Area of Science:

• Developmental Biology
• Molecular Signaling
• Genetics

Background:

• Wnt proteins are key extracellular signals in development and disease.
• Noncanonical Wnts, like Wnt5a, regulate morphogenetic movements independently of β-catenin.
• Wnt5a is known to interact with multiple receptors, including Ror, Ryk, and Frizzled, but their in vivo roles are unclear.

Purpose of the Study:

• To determine the in vivo role of Ror receptors in Wnt5a signaling.
• To identify downstream targets of Wnt5a-Ror interactions.
• To elucidate the contribution of Wnt5a-Ror signaling to embryonic development.

Main Methods:

• Loss-of-function experiments in mice.
• Analysis of embryonic phenotypes.
• Investigation of Dishevelled phosphorylation.

Main Results:

• Ror receptor deficiency recapitulates Wnt5a null mutant phenotypes.
• Ror receptors mediate Wnt5a-dependent processes in vivo.
• Dishevelled phosphorylation is identified as a direct target of Wnt5a-Ror signaling.
• Absence of Ror signaling causes defects in neuron axon branching and embryonic structures.

Conclusions:

• Wnt5a-Ror-Dishevelled signaling is a core noncanonical Wnt pathway.
• This pathway is essential for morphogenetic movements during embryogenesis.
• The Wnt5a-Ror pathway is conserved and critical for embryonic development.