Nucleoredoxin enhances stem cell transition to pituitary hormone-producing cells

Nucleoredoxin (Nxn) encodes a multi-functional enzyme with oxidoreductase activity that regulates many different signaling pathways in a redox-dependent manner. It is involved in a variety of cellular processes. Rare NXN mutations are reported in some individuals with recessive Robinow syndrome, which involves mesomelic short stature, craniofacial dysmorphisms, and incompletely penetrant heart and palate defects. Here we report that Nxn is expressed in the ventral diencephalon and Rathke’s pouch, and that Nxn deficient mice have pituitary dysmorphology, cleft palate, and craniofacial abnormalities. Nxn mutant mice exhibit altered WNT signaling and reduced progression of pituitary stem cells to hormone-producing cells. These results suggest that some patients with Robinow syndrome may have pituitary insufficiency and benefit from evaluation by endocrinologists. Embryonic pituitary glands were dissected at e14.5 and used for transcript analysis by scRNAseq