Nucleoredoxin regulates WNT signaling during pituitary stem cell differentiation.

Nucleoredoxin () encodes a multi-functional enzyme with oxidoreductase activity that regulates many different signaling pathways and cellular processes in a redox-dependent manner. Rare mutations are reported in individuals with recessive Robinow syndrome, which involves mesomelic skeletal dysplasia, short stature, craniofacial dysmorphisms, and incompletely penetrant heart and palate defects. Here we report that is expressed in the ventral diencephalon and developing pituitary gland, and that deficient mice have pituitary dysmorphology and craniofacial abnormalities that include defects in the skull base and cleft palate. mutant mice exhibit reduced WNT signaling and reduced differentiation of pituitary stem cells into hormone-producing cells. These results suggest patients with Robinow syndrome could benefit from evaluation by endocrinologists for pituitary structural imaging and hormone insufficiency.