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Primary Cilia are Required for Cell-Type Determination and Angiogenesis in Pituitary Development.
- Source :
-
Endocrinology [Endocrinology] 2024 Jul 01; Vol. 165 (8). - Publication Year :
- 2024
-
Abstract
- The functional maturation of the pituitary gland requires adequate cell differentiation and vascular network formation. Although spatiotemporal signaling and transcription factors are known to govern pituitary development, the involvement of primary cilia, nonmoving hair-like organelles, remains unclear. In this study, we uncovered the contribution of primary cilia to cell-type determination and vascular network formation during pituitary development. Homozygous knockout mice lacking a ciliary kinase, Dyrk2-/-, exhibit abnormalities in ciliary structure and pituitary hypoplasia, accompanied by varying degrees of failure in differentiation among all types of hormone-producing cells in the anterior lobe. Aberrations in cell differentiation in Dyrk2-/- mice arise from a decrease in the expression of crucial transcription factors, Lhx4, Lhx3, and Prop1, resulting from the inactivity of Hedgehog (Hh) signaling during the early stages of development. Furthermore, the loss of Dyrk2 results in vascular system abnormalities during the middle to late stages of development. Mechanistically, transcriptome analyses revealed the downregulation of vitronectin-integrin αvβ3-VEGFR2 signaling, essential for orchestrating vascular development. Collectively, our findings demonstrate that primary cilia play a pivotal role as critical regulators of cell survival, cell determination, and angiogenesis during pituitary gland development through the activation of Hh signaling. These findings expand our understanding of the potential link between pituitary dysfunction in human disorders and ciliopathies.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)
- Subjects :
- Animals
Mice
Angiogenesis
Hedgehog Proteins metabolism
Hedgehog Proteins genetics
Mice, Knockout
Signal Transduction
Transcription Factors metabolism
Transcription Factors genetics
Dyrk Kinases genetics
Cell Differentiation
Cilia metabolism
Cilia physiology
Neovascularization, Physiologic genetics
Neovascularization, Physiologic physiology
Pituitary Gland metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7170
- Volume :
- 165
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 39001875
- Full Text :
- https://doi.org/10.1210/endocr/bqae085