Heterogeneity of Sox2-expressing cells in mouse pituitary and their roles in postnatal gonadotroph differentiation

Postnatal differentiation of gonadotrophs from Sox2-expressing stem cells is essential for maturation of the hypothalamic-pituitary-gonadal axis, puberty, and reproduction. Here, we examined the differentiation and maintenance of gonadotrophs in developing and adult mice. Gonadotrophs and Sox2-expressing cells were identified by immunostaining, and gonadotrophs were also visualized by specific expression of the fluorescent protein tdTomato during embryonic and postnatal differentiation. Sox2-expressing cells are localized in the anterior parenchyma, marginal zone, and posterior pituitary, regardless of mouse age. Gonadotrophs are localized in the anterior parenchyma separate from Sox2-expressing cells. During the juvenile and prepubertal periods, cells in transition from Sox2 expression to tdTomato expression, as well as numerous differentiated gonadotrophs, were also present in the marginal zone. The size and distribution of the newly differentiated gonadotrophs were consistent with their migration into the parenchyma and maturation into a secretory cell type. Specific knockout of PI4-kinase A in gonadotrophs slowed their postnatal differentiation in the marginal zone, causing a significant reduction in the size of the gonadotroph population. This was accompanied by a progressive loss of specific gene expression in the residual gonadotrophs, leading to an increase in the number of dedifferentiated cells expressing tdTomato. Thus, Sox2 expressing cells in the marginal zone serve as stem cells for postnatal gonadotrophs, and the differentiation and maintenance of these cells require phosphoinositides derived by PI4-kinase A.