Endocrine Abstracts

Efnb2 plays an integral role during mouse development and in the adult stem cell niche. Efnb2 does encode for Ephrinb2 ligand which then binds to Eph receptor. Preliminary data suggest implication of Efnb2 in pituitary tumours and during normal pituitary embryogenesis. Currently, involvement of Eph:Ephrin signalling pathway in pituitary development is unknown. Better knowledge of Efnb2 in the pituitary will help to improve understanding of endocrine diseases. Deletion of Efnb2 in early pituitary progenitors was performed in vivo using the pituitary specific Hesx1 Cre-driver. Efnb2 is expressed in the pituitary from early development in stem cells; hence, it suggests a role in the maintenance of pituitary stem cells (PSCs). Conditional pituitary knockout mice exhibit severe hyperplasia and morphological abnormalities within the gland. To further understand molecular mechanism by which Efnb2 controls the pituitary, mRNA sequencing was done during early embryonic stages of pituitary development. Transcriptomic analyses include cell populations of Efnb2+/+ as well as Efnb2-/-. RNA sequencing reveals novel functions of Efnb2 in proliferation, epithelial integrity, and cell lineage commitment. Functional assays were then performed in order to validate these transcriptomic data. First, Efnb2 mutant mice exhibit increased mitotic index both in vivo and in vitro. Therefore, Efnb2 impacts cell proliferation of PSCs. Secondly, Efnb2 mutants present downregulation of epithelial integrity genes, which does result in abnormal epithelial mesenchymal transition (EMT). Importantly, Efnb2 regulates cell commitment. These events delay commitment as there is a significant reduction of Pomc1, Pit1 and Gsu, known pituitary cell lineage markers. In conclusion, Efnb2 is critical for pituitary development as it regulates the niche of PSCs. Our results demonstrate a novel role of Efnb2 in pituitary development by regulating cell proliferation, epithelial integrity, and cell lineage commitment of PSCs.