Three-dimensional studies of Prop1-expressing cells in the rat pituitary primordium of Rathke's pouch

Abstract

Pituitary embryonic development progresses daily toward terminal differentiation exhibiting quantitative and qualitative alterations regulated by signal molecules and transcription factors expressed under temporospatial control. In this study, we analyzed the heterogeneity of the cells in the pituitary primordium of embryonic day (E) 13.5. The three-dimensional structure of the Rathke's pouch was built up from measurements taken from multiple DAPI-stained sections and cell populations positive to stem/progenitor marker SOX2 and pituitary-specific transcription factor PROP1 were analyzed. The pituitary primordium (Rathke's pouch) of E13.5 showed a flattened discoid shape of about 500 μm in diameter and 200 μm depth in a dorsoventral axis and consisted in about 5,800 cells. Immunohistochemistry revealed that 0.3% of the cells in Rathke's pouch were SOX2-negative in the lateral region, whereas all cells at E12.5 were SOX2-positive. On E13.5, the shape and size of their nuclei showed a location-specific divergence: ellipsoid morphology in the median region and round morphology in the lateral region. Moreover, on E14.5, adrenocorticotropic-hormone-positive cells (the first hormone-producing cells appearing in the pituitary) contained round nuclei. These data suggest that differentiation to pituitary-hormone-producing cells from SOX2-negative cells starts in the lateral region between E12.5 and E13.5 and that the onset of differentiation is preceded by a change in nuclear shape.

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

“…The expression of the organ-specific factors Prop1 and Pit-1 may reveal a cell population at a committed precursor stage in the course of differentiation to a specific cell type (54). The mRNA levels of these markers displayed an interesting increase in the MZ and AP in AT and in the early and active lactancy groups.…”

“…The Sox9 progenitor marker, a member of the SoxE subfamily, is important in embryonic and postnatal development (9) and participates in differentiation programs by activation of tissue-specific genes (26). In the pituitary gland, it has been postulated that the transcription factor Prop1 might play a role as a trigger in the terminal differentiation process of progenitor cells, leading to the development of endocrine cells (53,54). Prop1 positively regulates the expression of the pituitary-specific transcription factor Pit-1, with this factor being critical for normal thyrotroph, somatotroph, and lactotroph development.…”

Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors

“…Other molecules play relevant roles in the development of the CNS, including the SOXB1 TFs (SOX1, SOX2 (Yako et al 2011) and SOX3 (Woods et al 2005)). SOX3 expression begins during early embryogenesis; recent studies have suggested that this gene must be expressed at a constant level because both increases and decreases in its expression are related to pituitary deficiencies and CNS malformations (Woods et al, 2005).…”

“…The WNT (Yako et al 2011) and SHH pathways (Fernandez-Rodriguez et al 2011) are important for proliferation regulation, while the BMP and FGF pathways are required for proliferation and for determining cellular migration (Kato et al 2010). Rathke's pouch formation is complete at approximately E10 .…”

“…Rathke's pouch formation is complete at approximately E10 . 5, and the pituitary precursor cells begin to express specific factors that determine their differentiation patterns (Yako et al 2011). This activation of distinct target genes occurs in response to the establishment of a dorsal-ventral gradient of FGF8 and a ventral-dorsal gradient of BMP2 (Ericson et al 1998).…”