ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study identifies the role of the Dlk1 gene dosage in controlling the size of the pituitary gland. Dlk1 is an imprinted gene—expression is based on parental origin—which plays a critical role in determining pituitary gland size.

The authors investigated how varying the dosage of Dlk1 affects pituitary size using genetically modified mice. Elegantly both, loss-of-function and overexpression of Dlk1 models were employed. Their findings suggest that Dlk1 dosage influences the balance between stem cell self-renewal and differentiation, in a precise developmental window frame impacting on the size of the anterior pituitary. They also discovered that the effects of Dlk1 on the pituitary are independent of overall body size, indicating a specific role in organ development rather than a general growth effect in body size.

The research has broader implications for understanding the endocrine system, particularly how imprinted genes like Dlk1 can affect organ size and hormone production, such as growth hormone (GH). Increased Dlk1 expression boosts stem cell replication and pituitary expansion without causing tumours, while Dlk1 loss reduces the organ’s size and GH production, pointing to the gene’s importance in postnatal development and homeostasis.

This study sheds light on the molecular mechanisms behind pituitary organ size, suggesting that Dlk1’s interaction with the WNT signalling pathway plays a significant role. Such insights are very important to understand pituitary homeostasis and pave the way to understanding pituitary-related diseases.