Paracrine FGF1 directs architecture and size

• 成果类型: Article
• 署名作者: Khetchoumian, Konstantin; Sochodolsky, Kevin; Lafont, Chrystel; Gouhier, Arthur; Bemmo, Amandine; Kherdjemil, Yacine; Kmita, Marie; Le Tissier, Paul; Mollard, Patrice; Christian, Helen; Drouin, Jacques
• 署名单位: Institut de Recherche Clinique de Montreal (IRCM); Universite de Montreal; Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Montpellier; Universite de Montreal; Institut de Recherche Clinique de Montreal (IRCM); Universite de Montreal; Institut de Recherche Clinique de Montreal (IRCM); University of Edinburgh; University of Oxford
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14630
• DOI: 10.1073/pnas.2410269121
• 发表日期: 2024-10-01
• 关键词: fibroblast-growth-factor; rat anterior-pituitary; cell-types; stem/progenitor cell; secretory granules; postnatal-period; proliferation; tpit; differentiation; deficiency

摘要

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 FGF1 as a corticotrope- specific Tpit dosage- dependent target gene responsible for these phenotypes. Consistently, genetic ablation of FGF1 in mice phenocopies pituitary hypoplasia and growth impairment observed in Tpit- deficient mice. These findings reveal FGF1 produced by the corticotrope cell network as an essential paracrine signaling molecule participating in pituitary architecture and size.