title: The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.
abstract: Metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. It has been very well established that amphibian metamorphosis is mainly controlled by Thyroid Hormone (TH). Here, we show that the heterochronic gene Lin28 is downregulated during Xenopus laevis metamorphosis. Lin28 overexpression before activation of TH signaling delays metamorphosis and inhibits the expression of TH target genes. The delay in metamorphosis is rescued by incubation with exogenous TH, indicating that Lin28 works upstream or parallel to TH. High-throughput analyses performed before any delay on metamorphosis or change in TH signaling showed that overexpression of Lin28 reduces transcript levels of several hormones secreted by the pituitary, including the Thyroid-Stimulating Hormone (TSH), and regulates the expression of proteins involved in TH transport, metabolism and signaling, showing that Lin28 disrupts TH function at different levels. Our data demonstrates that the role of Lin28 in controlling developmental transitions is evolutionary conserved and establishes a functional interaction between Lin28 and thyroid hormone function introducing a new regulatory step in perinatal development with implications for our understanding of endocrine disorders.
authors.affiliation: Center for Aging and Regeneration, Millennium Nucleus in Regenerative Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile; Universidad Andres Bello, Centro de Investigaciones Biomédicas, Facultad de Ciencias Biológicas, Autopista Concepción-Talcahuano 7100, Talcahuano, Chile. Electronic address: fernando.faunes@unab.cl.
authors.forename: Fernando
authors.initials: F
authors.lastname: Faunes
authors.affiliation: Center for Aging and Regeneration, Millennium Nucleus in Regenerative Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Gundermann
authors.affiliation: Center for Aging and Regeneration, Millennium Nucleus in Regenerative Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors.forename: Rosana
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: Center for Aging and Regeneration, Millennium Nucleus in Regenerative Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
authors.forename: Renzo
authors.initials: R
authors.lastname: Bruno
authors.affiliation: Center for Aging and Regeneration, Millennium Nucleus in Regenerative Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile. Electronic address: jlarrain@bio.puc.cl.
authors.forename: Juan
authors.initials: J
authors.lastname: Larraín
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D005121:Extremities / Q000601:surgery; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000235:genetics*; D008954:Models, Biological; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development*
chemical_list: C579731:Lin28a protein, Xenopus; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D013963:Thyroid Hormones; D029867:Xenopus Proteins
keywords: Heterochronic genes; Lin28; Metamorphosis; Pituitary; Thyroid hormone; Xenopus laevis