Paracrine FGF1 signaling directs pituitary architecture and size.

Abstract

Organ architecture is established during development through intricate cell-cell communication mechanisms, yet the specific signals mediating these communications often remain elusive. Here, we used the anterior pituitary gland that harbors different interdigitated hormone-secreting homotypic cell networks to dissect cell-cell communication mechanisms operating during late development. We show that blocking differentiation of corticotrope cells leads to pituitary hypoplasia with a major effect on somatotrope cells that directly contact corticotropes. Gene knockout of the corticotrope-restricted transcription factor Tpit results in fewer somatotropes, with less secretory granules and a loss of cell polarity, resulting in systemic growth retardation. Single-cell transcriptomic analyses identified <i>FGF1</i> as a corticotrope-specific <i>Tpit</i> dosage-dependent target gene responsible for these phenotypes. Consistently, genetic ablation of <i>FGF1</i> in mice phenocopies pituitary hypoplasia and growth impairment observed in <i>Tpit</i>-deficient mice. These findings reveal FGF1 produced by the corticotrope cell network as an essential paracrine signaling molecule participating in pituitary architecture and size.