MARS knockdown by shRNA abolished the ability of Hcy to increase β‐catenin levels (Fig 5D) and partially abrogated the ability of Hcy, but not HTL, to activate TCF targets (Fig EV2F), suggesting that Hcy sensing by MARSs is essential for Wnt/β‐catenin signalling, which in turn is required for normal neural tube and heart formation (Greene et al, 2009; Fossat et al, 2011; Zhao et al, 2014), regulation and likely for NTD development. This evidence concerns the gene HNF4A and neural tube defect.