Lhx4 Deficiency: Increased Cyclin-Dependent Kinase Inhibitor Expression and Pituitary Hypoplasia
Autor: | Sally A. Camper, Michelle L. Brinkmeier, Peter Gergics |
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Rok vydání: | 2015 |
Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Pituitary gland LIM-Homeodomain Proteins Mice Transgenic Hypopituitarism Mice Endocrinology Cyclin D1 Cyclin-dependent kinase Gene expression medicine Animals Progenitor cell Molecular Biology Original Research Cell Proliferation Homeodomain Proteins biology PITX2 Cell growth General Medicine Cell biology medicine.anatomical_structure Pituitary Gland biology.protein Cancer research LHX3 Transcription Factors |
Zdroj: | Molecular Endocrinology. 29:597-612 |
ISSN: | 1944-9917 0888-8809 |
Popis: | Defects in the Lhx4, Lhx3, and Pitx2 genes can cause combined pituitary hormone deficiency and pituitary hypoplasia in both humans and mice. Not much is known about the mechanism underlying hypoplasia in these mutants beyond generally increased cell death and poorly maintained proliferation. We identified both common and unique abnormalities in developmental regulation of key cell cycle regulator gene expression in each of these three mutants. All three mutants exhibit reduced expression of the proliferative marker Ki67 and the transitional marker p57. We discovered that expression of the cyclin-dependent kinase inhibitor 1a (Cdkn1a or p21) is expanded dorsally in the pituitary primordium of both Lhx3 and Lhx4 mutants. Uniquely, Lhx4 mutants exhibit reduced cyclin D1 expression and have auxiliary pouch-like structures. We show evidence for indirect and direct effects of LHX4 on p21 expression in αT3-1 pituitary cells. In summary, Lhx4 is necessary for efficient pituitary progenitor cell proliferation and restriction of p21 expression. |
Databáze: | OpenAIRE |
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