Lin28 paralogs regulate lung branching morphogenesis

Jihan K. Osborne, Melissa A. Kinney, Areum Han, Kemi E. Akinnola, Alena V. Yermalovich, Linda T. Vo, Daniel S. Pearson, Patricia M. Sousa, Sutheera Ratanasirintrawoot, Kaloyan M. Tsanov, Jessica Barragan, Trista E. North, Ross J. Metzger, George Q. Daley

Research output: Contribution to journalArticlepeer-review

Abstract

The molecular mechanisms that govern the choreographed timing of organ development remain poorly understood. Our investigation of the role of the Lin28a and Lin28b paralogs during the developmental process of branching morphogenesis establishes that dysregulation of Lin28a/b leads to abnormal branching morphogenesis in the lung and other tissues. Additionally, we find that the Lin28 paralogs, which regulate post-transcriptional processing of both mRNAs and microRNAs (miRNAs), predominantly control mRNAs during the initial phases of lung organogenesis. Target mRNAs include Sox2, Sox9, and Etv5, which coordinate lung development and differentiation. Moreover, we find that functional interactions between Lin28a and Sox9 are capable of bypassing branching defects in Lin28a/b mutant lungs. Here, we identify Lin28a and Lin28b as regulators of early embryonic lung development, highlighting the importance of the timing of post-transcriptional regulation of both miRNAs and mRNAs at distinct stages of organogenesis.

Original languageEnglish (US)
Article number109408
JournalCell Reports
Volume36
Issue number3
DOIs
StatePublished - Jul 20 2021
Externally publishedYes

Keywords

  • branching morphogenesis
  • Lin28a/Lin28b
  • lung development
  • post-transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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