Identification of a novel progenitor cell marker, grainyhead‐like 2 in the developing pituitary

Abstract

Background Pituitary stem/progenitor cells give rise to all of the endocrine cell types within the pituitary gland and are necessary for both development and gland homeostasis. Recent studies have identified several key factors that characterize the progenitor cell population. However, little is known about the factors that regulate progenitor cell differentiation and maintenance. Therefore, it is crucial to identify novel factors that help elucidate mechanisms of progenitor cell function in the developing pituitary. Our studies are the first to characterize the expression of Grainyhead-like 2 (GRHL2), a transcription factor known to regulate progenitor cell plasticity, in the developing pituitary. Results Our studies show GRHL2 expression is highest in the embryonic and early postnatal pituitary and is localized in pituitary progenitor cells. We demonstrate GRHL2 expression is changed in Notch2 cKO and Prop1 df/df mice, mouse models that display progenitor cell number defects. In addition, our studies indicate a potential relationship between Notch signaling and GRHL2 expression in the developing pituitary. Conclusions Taken together, our results indicate GRHL2 as a novel progenitor cell maker in the developing pituitary that may contribute to progenitor cell function and maintenance.

Pituitary stem cell regulation: who is pulling the strings?

“…In agreement, we detected higher Grhl2 gene expression in pituitary SOX2 eGFP+ stem cells as purified by FACS based on their Sox2-driven enhanced green fluorescent protein (eGFP) expression (Table 1). GHRL2 is also co-localized with the pituitary stem cell indicator E-cadherin and both markers concomitantly go down in Notch2 conditional knockout mice (Edwards et al 2016). In other tissues, GHRL2 has been found to induce the expression of Cdh1 (encoding E-cadherin) (Werth et al 2010, which may explain their colocalization in pituitary stem cells.…”

“…In the stem cell population (SC-SP) of the adult pituitary, Hey1 seems to be the main NOTCH pathway target component (Table 1), whereas Hes6, in general, involved in NOTCH-driven differentiation (Bae et al 2000), is higher expressed in the non-SP 'main population' (MP) (Chen et al 2006). Recently, grainyheadlike 2 (Grhl2) has been advanced as another direct NOTCH downstream target gene in the pituitary (Edwards et al 2016). Its expression is mainly restricted to SOX2 + cells, both in the marginal zone and in the parenchyma.…”

Medication for Acromegaly Reduces Expression of MUC16, MACC1 and GRHL2 in Pituitary Neuroendocrine Tumour Tissue

“…It was involved in the regulation of various developmental processes such as closure of the neural tube and the regulation of progenitor cell functions during the development of the pituitary gland. GRHL2 is expressed in pituitary progenitor cells and in mice with decreased pituitary progenitor cell numbers ( 37 ). GRHL2 has been implicated in many cancers such as breast, lung, colorectal, gastric, ovarian, and prostate.…”

Transcriptional mechanisms coordinating tight junction assembly during epithelial differentiation

“…In mouse embryos, the transcription factor GRHL2 strongly localizes to E‐cadherin–expressing epithelia, such as the surface ectoderm, the gut tube endoderm, and the otic vesicle . Robust GRHL2 expression is also observed in the lung epithelium, the cholangiocytes of the liver, the epithelia of the distal nephron and collecting duct, and the pituitary in embryonic development and adulthood . In the context of barrier formation, GRHL2 is thus far the best characterized Grh family member.…”

“…50,57,58 Robust GRHL2 expression is also observed in the lung epithelium, the cholangiocytes of the liver, the epithelia of the distal nephron and collecting duct, and the pituitary in embryonic development and adulthood. 57,[59][60][61][62][63] In the context of barrier formation, GRHL2 is thus far the best characterized Grh family member. It plays critical roles in epithelial morphogenesis via regulation of apical junction formation, lumen expansion, and the suppression of EMT.…”