Interactions between pituitary cell lineages direct tissue architecture and size
Organ architecture is established during development through specific cell:cell contacts. The mechanisms responsible for these specific cell interactions remain poorly understood. In order to address this question, we used the anterior pituitary gland that harbors five different and interdigitated hormone-secreting homotypic cell networks. We now report that blocking differentiation of the first lineage to arise during pituitary development, the corticotrope cells, leads to pituitary hypoplasia with a major effect on the somatotrope cells that are fewer, with less secretory granules and a loss of cell polarity. These somatotrope cell phenotypes are dependent on gene dosage for the corticotrope-restricted transcription factor Tpit. In addition, the Tpit-deficient pituitary is hyper-vascularized. Single cell transcriptomics identifiy corticotrope and somatotrope regulatory and signaling pathways that may underlie cell:cell communications responsible for these phenotypes. Collectively, the results indicate that the corticotrope cell network is an important paracrine signalling center regulating pituitary architecture and size. Overall design: scRNA-seq in mouse pituitary