Abstract
Nucleoredoxin (Nxn) encodes a multi-functional enzyme with oxidoreductase activity that regulates many different signaling pathways and cellular processes in a redox-dependent manner. Rare NXN 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 Nxn is expressed in the ventral diencephalon and developing pituitary gland, and that Nxn deficient mice have pituitary dysmorphology and craniofacial abnormalities that include defects in the skull base and cleft palate. Nxn 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.
Highlights
Nxn deficiency causes neonatal lethality, cleft palate, craniofacial abnormalities, and other structural birth defects.
Nxn deficiency causes pituitary dysmorphology.
Analysis of scRNA seq reveals delayed trajectory during early pituitary cell differentiation.
Nxn deficiency reduces canonical and non-canonical Wnt signaling in developing pituitary glands.
Nxn deficiency reduces stem cell differentiation into pituitary hormone-producing cells.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
rollerm{at}umich.edu, leonard.cheung{at}stonybrook.edu, soconnell{at}tutanota.com, dianakg{at}email.sc.edu, ec01rhoa{at}siena.edu, scamper{at}umich.edu
Figure 4 is revised to include additional data.