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Minibrain and Wings apart control organ growth and tissue patterning through down-regulation of Capicua

Liu Yang1, Sayantanee Paul1, Kenneth G Trieu1

  • 1Department of Biology, University of Massachusetts, Boston, MA 02125;

Proceedings of the National Academy of Sciences of the United States of America
|September 8, 2016
PubMed

Insights

Minibrain (Mnb) and Wings apart (Wap) inhibit the Capicua (Cic) repressor, controlling organ growth and tissue patterning. This newly discovered pathway offers insights into Cic regulation beyond the ERK pathway.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cancer Biology

Background:

  • Capicua (Cic) is a transcriptional repressor regulating tissue patterning and organ growth.
  • Cic acts downstream of receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) signaling.
  • Regulation of Cic activity in diverse cellular contexts is not fully understood.

Purpose of the Study:

  • To investigate novel regulatory mechanisms controlling Capicua (Cic) activity.
  • To identify proteins interacting with and modulating Cic function.
  • To understand Cic's role in organ development and tissue patterning.

Main Methods:

  • Co-immunoprecipitation to detect protein interactions.
  • In vitro kinase assays to assess phosphorylation.
  • In vivo studies in Drosophila to analyze effects on organ growth and patterning.

Main Results:

  • Minibrain (Mnb) kinase and Wings apart (Wap) adaptor protein physically interact with Cic.
  • Mnb and Wap phosphorylate Cic, inhibiting its transcriptional repressor activity.
  • Down-regulation of Cic by Mnb/Wap is crucial for organ growth (wings, eyes, brain) and wing tissue patterning.
  • This Mnb/Wap-mediated inhibition of Cic is independent of ERK signaling.

Conclusions:

  • A novel pathway involving Mnb and Wap inhibits Cic activity, distinct from ERK-mediated regulation.
  • Cic integrates multiple upstream signals for proper tissue patterning and organ growth.
  • The findings suggest DYRK1A (Mnb ortholog) may regulate CIC in human oligodendroglioma, linking developmental pathways to cancer.
Keywords:
DYRK1Acapicuaminibrainorgan growthtissue patterning

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