PRRX1 and PRRX2 distinctively participate in pituitary organogenesis and a cell-supply system

Paired-related homeobox transcription factors, PRRX1 and PRRX2, are known to be important factors for craniofacial and limb morphogenesis. We recently cloned Prrx2 from the porcine adult pituitary cDNA library and found that only PRRX1 is present in the rat embryonic pituitary. In this study, we re-investigated the temporospatial expression and localization of PRRX1 and PRRX2 in the rat pituitary throughout life. The persistent expression of Prrx1 was ascertained after the middle stage of embryonic development, whereas significant expression of Prrx2 was found only in the postnatal pituitary. Immunohistochemistry confirmed that PRRX1-positive cells appeared inside the pituitary on embryonic day 16.5 in the marginal cell layer (MCL), a pituitary stem/progenitor cell niche, and the expanding parenchyma of the anterior pituitary. In contrast, PRRX2-positive cells first appeared in the anterior lobe and intermediate lobe sides of the MCL around postnatal day 30 when the postnatal pituitary growth wave had almost terminated. Immunostaining for PRRX1 with a stem/progenitor cell marker SOX2, a pituitary progenitor marker PROP1, or pituitary hormones revealed that PRRX1 localized in cells in the transition process from the multipotent progenitor stage to the early stage of terminal differentiation throughout life. PRRX2 emerged in cells positive for SOX2 but negative for PROP1 in the anterior and intermediate lobe sides of the postnatal MCL. Thus, PRRX1 and PRRX2 might participate distinctly in pituitary organogenesis and the postnatal cell-supply system.