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

Anna R. Duncan, Delfina P. González, Florencia del Viso, Andrew Robson, Mustafa K. Khokha, John N. Griffin

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalDevelopmental Biology
Issue number1
Early online date6 Aug 2019
Publication statusPublished - 1 Dec 2019
Externally publishedYes


  • AGMO
  • Alkylglycerol monooxygenase
  • Congenital heart disease
  • Ether lipids
  • Heterotaxy
  • TMEM195
  • Wnt
  • Xenopus

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