The Role of AGMO – alkylglycerol monooxygenase – in development

The canonical Wnt pathway is a potent signalling system that regulates numerous processes during embryonic development, including cell fate determination, migration, polarity, proliferation, and apoptosis, as well as stem cell biology and adult tissue homeostasis. Dysregulated Wnt signalling contributes to many diseases, including birth defects, neurodegeneration, and cancers. As a result, investigation of the Wnt pathway, and identification of Wnt regulators, is considered a research priority.

Lipid modifications are rapidly emerging as critical regulators of nearly every step in the canonical Wnt pathway. However, the nature, regulation and significance of such modifications remains poorly understood. Alkylglycerol monooxygenase (AGMO), the only enzyme known to cleave the O-alkyl ether bond in alkylglycerols, has recently been shown to be a critical regulator of Wnt signalling in the embryo. Ether lipids were not previously implicated in Wnt signalling or embryo formation.

In this project the student will identify and investigate agmo requirements during Xenopus embryogenesis, and determine precisely how agmo regulates the canonical Wnt signalling pathway. These studies will transform our understanding of the role ether lipids play in development and disease, opening up new avenues of investigation.

References

Dean JM, Lodhi IJ, (2018). Structural and functional roles of ether lipids. Protein Cell 9, 196–206.

Duncan AR, González DP, Del Viso F, Robson A, Khokha K, Griffin J. (2019). Alkylglycerol monooxygenase, a heterotaxy candidate gene, regulates left-right patterning via Wnt signalling. Developmental Biology 456: 1–7

Godden A, Antonaci M, Ward NJ, Van der Lee M, Abu-Daya A, Guille M and Wheeler GN. (2022). An efficient miRNA knockout approach using CRISPR-Cas9 in Xenopus. Developmental Biology. 483, p. 66-75

Steinhart, Z. and Angers, S. 2018. Wnt signalling in development and tissue homeostasis. Development, 145(11) doi: 10.1242/dev.146589

Watschinger K, Werner ER, (2013). Alkylglycerol monooxygenase. IUBMB Life 65, 366–372.