Rapid transition of NESTIN-expressing dividing cells from PROP1-positive to PIT1-positive advances prenatal pituitary development.

We recently reported that the quantitative and qualitative transition of stem/progenitor cells occurs by the acquisition of a novel mechanism in the terminal differentiation during postnatal development of the anterior pituitary. We hypothesised that this novel mechanism is an alteration of a cell supply system accompanying proliferation of the progenitor cells. In the present study, we examined the proliferation activities of progenitor cells by indication of the expression of Nestin, a marker of rapidly dividing progenitor cells, aiming to verify our hypothesis and to resolve another outstanding issue regarding whether the Nestin gene is expressed in the pituitary. We found that NESTIN-positive dividing cells certainly exist in the pituitary through all stages of development. Almost all of the PROP1-positive progenitor cells express Nestin in early embryonic pituitary development. Thereafter, Nestin-expressing dividing cells involved in the cell supply system transfer from PROP1-positive progenitor cells to committed progenitor cells, such as PIT1-positive cells, on neonatal pituitary development. Furthermore, our data, together with the findings of previous studies on cell lineage tracing analyses using Nestin-Cre mice derived by the central nervous system (CNS)-specific Nestin promoter, suggest that at least two regulation systems for Nestin-expression exist in the pituitary, with the majority of these not being CNS-specific.