Alkylglycerol monooxygenase, a heterotaxy candidate gene, regulates left-right patterning via Wnt signaling

Duncan, Anna R., González, Delfina P., del Viso, Florencia, Robson, Andrew, Khokha, Mustafa K. and Griffin, John N. (2019) Alkylglycerol monooxygenase, a heterotaxy candidate gene, regulates left-right patterning via Wnt signaling. Developmental Biology, 456 (1). pp. 1-7. ISSN 0012-1606

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Abstract

Congenital heart disease (CHD) is a major cause of morbidity in the pediatric population yet its genetic and molecular causes remain poorly defined. Previously, we identified AGMO as a candidate heterotaxy disease gene, a disorder of left-right (LR) patterning that can have a profound effect on cardiac function. AGMO is the only known alkylglycerol monooxygenase, an orphan tetrahydrobiopterin dependent enzyme that cleaves the ether linkage in alkylglycerols. However, whether AGMO plays a role in LR patterning was unexplored. Here we reveal that Agmo is required for correct development of the embryonic LR axis in Xenopus embryos recapitulating the patient's heterotaxy phenotype. Mechanistically, we demonstrate that Agmo is a regulator of canonical Wnt signaling, required during gastrulation for normal formation of the left – right organizer. Mutational analysis demonstrates that this function is dependent on Agmo's alkylglycerol monooxygenase activity. Together, our findings identify Agmo as a regulator of canonical Wnt signaling, demonstrate a role for Agmo in embryonic axis formation, and provide insight into the poorly understood developmental requirements for ether lipid cleavage.

Item Type: Article
Uncontrolled Keywords: agmo,alkylglycerol monooxygenase,congenital heart disease,ether lipids,heterotaxy,tmem195,wnt,xenopus,molecular biology,developmental biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1312
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Depositing User: LivePure Connector
Date Deposited: 03 Apr 2020 00:45
Last Modified: 28 Aug 2020 23:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/74694
DOI: 10.1016/j.ydbio.2019.07.019

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