The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function

Fernando Faunes, Daniel G. Gundermann, Rosana Muñoz, Renzo Bruno, Juan Larraín

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)142-151
Number of pages10
JournalDevelopmental Biology
Volume425
Issue number2
DOIs
Publication statusPublished - 15 May 2017

Keywords

  • Heterochronic genes
  • Lin28
  • Metamorphosis
  • Pituitary
  • Thyroid hormone
  • Xenopus laevis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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