MicroRNA-7a2 is required for the development of pituitary stem cells.

Abstract

The pituitary gland is inhabited by a subpopulation of SOX2+ stem cells. However, the regulatory mechanisms underlying pituitary stem cell development remain poorly understood. Here, we demonstrate that microRNA-7a (miR-7a) is enriched in the developing pituitary and is spatiotemporally expressed in the pituitary stem cells. Constitutive deletion of miR-7a2 in mice results in pituitary dysplasia emerging during birth, which is primarily manifested as malformed anterior lobes. Using immunofluorescence, immunohistochemistry or in situ hybridization, we observe that the specification of hormone-expressing cells is not impeded post miR-7a2 deletion at birth, although the terminal differentiation of gonadotropes is inhibited. Further investigation of neonatal and adult pituitaries in miR-7a2 knockout mice reveals an expansion of the SOX2+ pituitary stem cell compartment. The inhibition of epithelial-mesenchymal like transition seems to be responsible for this phenotype, rather than abnormal proliferation or apoptosis. Furthermore, our data suggest that Gli3 and Ckap4 are potential targets of miR-7a in pituitary stem cells. In summary, our results identify miR-7a2 as a crucial factor involved in pituitary stem cell development.