title: The Krüppel-like factor 4 controls biosynthesis of thyrotropin-releasing hormone during hypothalamus development.
abstract: Embryonic neurogenesis is controlled by the activation of specific genetic programs. In the hypothalamus, neuronal thyrotropin-releasing hormone (TRH) populations control important physiological process, including energy homeostasis and autonomic function; however, the genetic program leading to the TRH expression is poorly understood. Here, we show that the Klf4 gene, encoding the transcription factor Krüppel-like factor 4 (Klf4), was expressed in the rat hypothalamus during development and regulated Trh expression. In rat fetal hypothalamic cells Klf4 regulated Trh promoter activity through CACCC and GC motifs present on the Trh gene promoter. Accordingly, hypothalamic Trh expression was down-regulated at embryonic day 15 in the Klf4(-/-) mice resulting in diminished bioactive peptide levels. Although at the neonatal stage the Trh transcript levels of the Klf4(-/-) mice were normal, the reduction in peptide levels persisted. Thus, our data indicate that Klf4 plays a key role in the maturation of TRH expression in hypothalamic neurons.
authors.affiliation: Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62271, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Monter
authors.forename: Miriam
authors.initials: M
authors.lastname: Martínez-Armenta
authors.forename: Amaya
authors.initials: A
authors.lastname: Miquelajauregui
authors.forename: Mayra
authors.initials: M
authors.lastname: Furlan-Magaril
authors.forename: Alfredo
authors.initials: A
authors.lastname: Varela-Echavarría
authors.forename: Félix
authors.initials: F
authors.lastname: Recillas-Targa
authors.forename: Víctor
authors.initials: V
authors.lastname: May
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Charli
authors.forename: Leonor
authors.initials: L
authors.lastname: Pérez-Martínez
mesh_terms: D000818:Animals; D001483:Base Sequence; D018507:Gene Expression Regulation, Developmental; D007031:Hypothalamus / Q000196:embryology* / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016329:Sp1 Transcription Factor; D013973:Thyrotropin-Releasing Hormone