The mechanism by which glucose stimulates the expression of Alx3 is unknown, but it appears not to be specific of embryonic cells. In the adult organism, expression of Alx3 in glucagon-producing cells of the pancreatic islets is also stimulated by glucose. In that case, increased levels of ALX3 in response to elevated glucose result in transcription factor interactions that lead to down-regulation of the glucagon gene, closing a negative feed back loop important for the maintenance of glucose homeostasis36. Thus, Alx3 emerges as an important glucose sensor to protect the organism against the harmful effects of hyperglycaemia. In the present study, Alx3 deficiency in mouse embryos developing in diabetic mothers resulted in increased oxidative stress, rendering them more vulnerable to congenital malformations.