The gene encoding the homeodomain transcription factor ALX3 is expressed in mesenchymal cells in mouse mid gestation embryos and regulates important developmental processes30–33. Recessive mutations in this gene in humans or its deficiency in mice result in craniofacial malformations as well as in cranial neural tube defects accompanied by increased apoptosis in the forehead mesenchyme32, 34. In mice, this phenotype exhibits a characteristic incomplete penetrance so that a considerable proportion of Alx3-deficient embryos are apparently normal and viable32, 33. In adult mice, Alx3 is expressed in pancreatic islets, and its deficiency leads to apoptosis of islet cells and alterations in glucose homeostasis without reaching overt diabetes35, 36. Based on these observations and on the association between Alx3-deficiency and apoptosis32, 35, we investigated whether Alx3-deficient embryos are more vulnerable to the harmful effects of hyperglycaemia during diabetic pregnancy.