Spatiotemporal distribution of Delta-like protein 1 during mouse pituitary ontogeny and its relationship with differentiating endocrine cell populations

Abstract

Delta-like protein 1 (DLK1) is a transmembrane protein involved in the regulation of cellular differentiation and stem cell maintenance in several tissues, including the pituitary gland. Although DLK1 expression has been reported in the adult pituitary, its spatiotemporal distribution during mouse pituitary development remains incompletely characterized. The aim of this study was to analyse the distribution of DLK1 during embryonic and postnatal development of the mouse pituitary gland and to characterize its relationship with hormone-producing cell populations. Immunohistochemistry was performed in Swiss albino mice from embryonic day 9.5 (e9.5) to postnatal day 15 (p15). Double immunofluorescence was used at e18.5 and p15 to examine the association of DLK1 immunoreactivity with ACTH-, TSH-, GH-, FSH- and PRL-producing cells. DLK1 immunoreactivity was detected from the earliest stages of pituitary development in Rathke`s pouch and the ventral diencephalon. During embryonic development, DLK1-ir cells were widely distributed throughout adenohypophyseal and neurohypophyseal primordia. As development progressed, DLK1 immunoreactivity became progressively regionalized within the anterior, intermediate and tuberal lobes, as well as in the median eminence of the hypothalamus and the posterior pituitary lobe. Colocalization of DLK1 with each of the hormone-producing cell populations analysed was observed at e18.5 and p15. Semiquantitative analysis at p15 indicated that approximately 32% of adenohypophyseal cells were DLK1-immunoreactive. These findings provide a detailed description of the spatiotemporal distribution of DLK1 during mouse pituitary ontogeny and suggest that DLK1 immunoreactivity is associated with differentiating endocrine cell populations throughout pituitary development.