Endocrine Abstracts

Efnb2 plays an integral role during mouse development, specifically in angiogenesis and stem cell regulation. Efnb2 encodes for Ephrinb2 ligand that binds to Eph receptor. Preliminary data suggest implications of Efnb2 in pituitary tumors. The involvement of Eph:Ephrin signaling pathway in pituitary development is currently unknown. Better knowledge of Efnb2 in the pituitary will improve the understanding of endocrine disease. Therefore, a pituitary-specific Cre-driver (Hesx1 ^Cre ) was used to genetically delete Efnb2 in early pituitary progenitors in vivo. Our experiments show that Efnb2 recapitulates the expression of pituitary stem cells (PSCs) during embryogenesis. Deletion of Efnb2 leads to abnormal morphology of the gland, specifically impacting the niche of PSCs which suggests its involvement in PSCs maintenance. We then performed mRNA sequencing during early pituitary development stages to elucidate the molecular role of Efnb2 in the pituitary. This transcriptomic analysis revealed novel functions of Efnb2 in cell proliferation, epithelial integrity and cell lineage commitment. Validation experiments of transcriptomic analyses confirm that Efnb2 negatively regulates PSC proliferation in vivo and in vitro. Efnb2 mutants exhibit increased mitotic index, hyper-proliferating in the niche of PSC. Additionally, Efnb2 mutants present downregulation of epithelial integrity leading to abnormalities in epithelial-mesenchymal transition (EMT) of the PSC niche. Moreover, mutant mice present a significant reduction in the expression of pituitary lineage commitment markers (Pit1, Pomc1 and Gsu). These results demonstrate that Efnb2 is critical for pituitary development and further regulates the niche of PSC.