Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

Gen Shinoda, Ng Shyh-Chang, T. Yvanka De Soysa, Hao Zhu, Marc T. Seligson, Samar P. Shah, Nora Abo-Sido, Akiko Yabuuchi, John P. Hagan, Richard I. Gregory, John M. Asara, Lewis C. Cantley, Eric G. Moss, George Q. Daley

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue- specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling.

Original languageEnglish (US)
Pages (from-to)1563-1573
Number of pages11
JournalStem Cells
Volume31
Issue number8
DOIs
StatePublished - Aug 1 2013

Keywords

  • Diabetes
  • Dwarfism
  • Glucose metabolism
  • Growth
  • Let-7
  • Lin28a
  • Lin28b
  • MTOR

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism'. Together they form a unique fingerprint.

  • Cite this

    Shinoda, G., Shyh-Chang, N., Yvanka De Soysa, T., Zhu, H., Seligson, M. T., Shah, S. P., Abo-Sido, N., Yabuuchi, A., Hagan, J. P., Gregory, R. I., Asara, J. M., Cantley, L. C., Moss, E. G., & Daley, G. Q. (2013). Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism. Stem Cells, 31(8), 1563-1573. https://doi.org/10.1002/stem.1423