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Updated: Oct 15, 2026
Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
Ryk-deficient mice exhibit craniofacial defects associated with perturbed Eph receptor crosstalk
M M Halford1, J Armes, M Buchert
1Ludwig Institute for Cancer Research, PO Box 2008, Royal Melbourne Hospital, Victoria, Australia.
Abstract:
Secondary palate formation is a complex process that is frequently disturbed in mammals, resulting in the birth defect cleft palate. Gene targeting has identified components of cytokine/growth factor signalling systems such as Tgf-alpha/Egfr, Eph receptors B2 and B3 (Ephb2 and Ephb3, respectively), Tgf-beta2, Tgf-beta3 and activin-betaA (ref. 3) as regulators of secondary palate development. Here we demonstrate that the mouse orphan receptor 'related to tyrosine kinases' (Ryk) is essential for normal development and morphogenesis of craniofacial structures including the secondary palate. Ryk belongs to a subclass of catalytically inactive, but otherwise distantly related, receptor protein tyrosine kinases (RTKs). Mice homozygous for a null allele of Ryk have a distinctive craniofacial appearance, shortened limbs and postnatal mortality due to feeding and respiratory complications associated with a complete cleft of the secondary palate. Consistent with cleft palate phenocopy in Ephb2/Ephb3-deficient mice and the role of a Drosophila melanogaster Ryk orthologue, Derailed, in the transduction of repulsive axon pathfinding cues, our biochemical data implicate Ryk in signalling mediated by Eph receptors and the cell-junction-associated Af-6 (also known as Afadin). Our findings highlight the importance of signal crosstalk between members of different RTK subfamilies.
Insights
The orphan receptor Ryk is crucial for craniofacial development, including secondary palate formation. Its absence causes cleft palate and other defects in mice, highlighting Ryk
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Secondary palate formation is vital for mammalian development and frequently disrupted, leading to cleft palate.
- Several signaling pathways, including Tgf-alpha/Egfr and Eph receptors, are known regulators of palate development.
Purpose of the Study:
- To investigate the role of the orphan receptor Ryk in craniofacial development and secondary palate formation.
- To elucidate the molecular mechanisms underlying Ryk's function in these processes.
Main Methods:
- Gene targeting to create Ryk-deficient mice.
- Phenotypic analysis of craniofacial structures, limbs, and survival.
- Biochemical assays to explore signaling pathways involving Ryk.
Main Results:
- Ryk-deficient mice exhibit severe craniofacial abnormalities, including complete cleft palate, shortened limbs, and postnatal mortality.
- Ryk is essential for normal morphogenesis of craniofacial structures.
- Biochemical data suggest Ryk signaling interacts with Eph receptors and Af-6 (Afadin).
Conclusions:
- The orphan receptor Ryk is indispensable for normal craniofacial development and secondary palate formation.
- Ryk plays a critical role in signaling pathways, potentially involving crosstalk with Eph receptor family members.
- Dysregulation of Ryk signaling may contribute to congenital defects like cleft palate.
