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Studying Wnt Signaling During Patterning of Conducting Airways
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Alkylglycerol monooxygenase, a heterotaxy candidate gene, regulates left-right patterning via Wnt signaling

Anna R Duncan1, Delfina P González1, Florencia Del Viso1

  • 1Pediatric Genomics Discovery Program, Department of Pediatrics and Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT, 06510, USA.

Developmental Biology
|August 10, 2019
PubMed

Insights

Alkylglycerol monooxygenase (AGMO) is crucial for embryonic left-right axis formation by regulating Wnt signaling. This finding offers new insights into congenital heart disease causes.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Congenital heart disease (CHD) is a significant cause of pediatric morbidity with poorly understood genetic underpinnings.
  • Heterotaxy, a disorder of left-right (LR) patterning affecting cardiac function, has candidate genes like AGMO.
  • AGMO, an alkylglycerol monooxygenase, had an unexplored role in LR patterning.

Purpose of the Study:

  • To investigate the role of AGMO in embryonic left-right (LR) axis development.
  • To elucidate the molecular mechanisms by which AGMO influences LR patterning.
  • To determine if AGMO's enzymatic activity is essential for its developmental function.

Main Methods:

  • Utilized Xenopus embryos to study embryonic LR axis development.
  • Assessed the impact of Agmo on canonical Wnt signaling during gastrulation.
  • Performed mutational analysis to link AGMO's enzymatic activity to its function.

Main Results:

  • Agmo is essential for correct embryonic LR axis development in Xenopus, mirroring heterotaxy phenotypes.
  • Agmo regulates canonical Wnt signaling, specifically during gastrulation for left-right organizer formation.
  • AGMO's alkylglycerol monooxygenase activity is critical for its role in embryonic axis formation.

Conclusions:

  • AGMO is identified as a novel regulator of canonical Wnt signaling.
  • AGMO plays a vital role in embryonic left-right axis formation.
  • Ether lipid cleavage by AGMO is important for developmental processes, offering insights into CHD etiology.

Keywords:
AGMOAlkylglycerol monooxygenaseCongenital heart diseaseEther lipidsHeterotaxyTMEM195WntXenopus

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