MicroRNAs regulate pituitary development, and microRNA 26b specifically targets lymphoid enhancer factor 1 (Lef-1), which modulates pituitary transcription factor 1 (Pit-1) expression.
To understand the role of microRNAs (miRNAs) in pituitary development, a group of pituitary-specific miRNAs were identified, and Dicer1 was then conditionally knocked out using the Pitx2-Cre mouse, resulting in the loss of mature miRNAs in the anterior pituitary. The Pitx2-Cre/Dicer1 mutant mice demonstrate growth retardation, and the pituitaries are hypoplastic with an abnormal branching of the anterior lobe, revealing a role for microRNAs in pituitary development. Growth hormone, prolactin, and thyroid-stimulating hormone β-subunit expression were decreased in the Dicer1 mutant mouse, whereas proopiomelanocortin and luteinizing hormone β-subunit expression were normal in the mutant pituitary. Further analyses revealed decreased Pit-1 and increased Lef-1 expression in the mutant mouse pituitary, consistent with the repression of the Pit-1 promoter by Lef-1. Lef-1 directly targets and represses the Pit-1 promoter. miRNA-26b (miR-26b) was identified as targeting Lef-1 expression, and miR-26b represses Lef-1 in pituitary and non-pituitary cell lines. Furthermore, miR-26b up-regulates Pit-1 and growth hormone expression by attenuating Lef-1 expression in GH3 cells. This study demonstrates that microRNAs are critical for anterior pituitary development and that miR-26b regulates Pit-1 expression by inhibiting Lef-1 expression and may promote Pit-1 lineage differentiation during pituitary development.
Zhang
Zichao
Z
Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
Florez
Sergio
S
Gutierrez-Hartmann
Arthur
A
Martin
James F
JF
Amendt
Brad A
BA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D037101:Luteinizing Hormone, beta Subunit / Q000096:biosynthesis / Q000235:genetics; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010903:Pituitary Gland, Anterior / Q000196:embryology* / Q000254:growth & development; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D011388:Prolactin / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology*; D043244:Ribonuclease III; D037322:Thyrotropin, beta Subunit / Q000096:biosynthesis / Q000235:genetics; D050817:Transcription Factor Pit-1 / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097577:Homeobox Protein PITX2
D053487:DEAD-box RNA Helicases; D004722:Endoribonucleases; D018398:Homeodomain Proteins; D037101:Luteinizing Hormone, beta Subunit; D051821:Lymphoid Enhancer-Binding Factor 1; D035683:MicroRNAs; D011333:Pro-Opiomelanocortin; D011388:Prolactin; D043244:Ribonuclease III; D037322:Thyrotropin, beta Subunit; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C497574:Lef1 protein, mouse; C494185:Pou1f1 protein, mouse; C509781:Dicer1 protein, mouse
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