Endocrine Abstracts

The pituitary progenitors are responsible for generating a fully functional endocrine organ during embryonic development. They also preserve potency, to maintain the homoeostasis in the adult pituitary, being able to respond to endocrine challenges, such as pregnancy or obesity. But the main players of this complex process remain elusive. Eph-Ephrins have been implicated in an increasing number of physiological functions such as axon-guidance, eye field segregation from neural plate, tissue boundary formation, cell migration, angiogenesis and more recently stem cell maintenance and differentiation in the colon and mammary gland. However, the EprhinB:EphB signalling pathway in hypothalamic-pituitary function is not known. Using a transgenic line that expresses GFP under the EphrinB2 (Efnb2) genetic locus we observed that cells expressing Efnb2 are localised in the pituitary progenitor of the anterior pituitary. We found Efnb2 co-expressed with known PPSCs markers Sox2/Sox9 during embryogenesis and this expression continues in adulthood, suggesting a role in adult pituitary homoeostasis. Conditional genetic removal of Efnb2 in the undifferentiated precursor using a Cre-pituitary line, results in significant pituitary abnormalities, comprising multiple bifurcations hyperplasia of the anterior pituitary gland. These data suggest for the first time, that Efnb2 is a critical regulator of pituitary development and could have an effect on hypothalamic-pituitary body endocrine regulations. Interestingly a proportion of Efnb2 Knock-out animals exhibit features of congenital hypopituitarism, such as dwarfism and eye abnormalities suggesting that, in this physiological context, Efnb2 could be a candidate gene for rare unknown conditions such Septo-Optic Dysplasia.