title: Lhx4 deficiency: increased cyclin-dependent kinase inhibitor expression and pituitary hypoplasia.
abstract: 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.
authors: Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109.
authors: Peter
authors: P
authors: Gergics
authors: Michelle L
authors: ML
authors: Brinkmeier
authors: Sally A
authors: SA
authors: Camper
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007018:Hypopituitarism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C493957:Cdkn1a protein, mouse; C094898:Lhx3 protein; C108538:Lhx4 protein, mouse