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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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Nerfin-1 represses transcriptional output of Hippo signaling in cell competition

Pengfei Guo1, Chang-Hyun Lee1, Huiyan Lei1

  • 1Department of Physiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States.

Elife
|March 23, 2019
PubMed

Insights

Scientists discovered Nerfin-1, a repressor that limits tissue growth by inhibiting the Scalloped-Yorkie complex. Loss of Nerfin-1 promotes cell competition, and its mammalian counterpart, INSM1, also represses Hippo pathway activity.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • The Hippo pathway controls tissue growth by regulating transcription factors.
  • The Scalloped (Sd)-Yorkie (Yki) complex is a key mediator of Hippo signaling, promoting gene expression for growth.
  • Understanding the regulation of the Sd-Yki complex is crucial for comprehending tissue homeostasis.

Purpose of the Study:

  • To identify novel regulators of the Scalloped (Sd)-Yorkie (Yki) complex.
  • To investigate the role of Nerfin-1 in Hippo pathway signaling and tissue growth.
  • To explore the conserved function of mammalian INSM1 in regulating TEAD-YAP activity.

Main Methods:

  • Biochemical assays to determine Nerfin-1 binding to Sd.
  • Analysis of tissue growth upon ectopic Nerfin-1 expression in Drosophila.
  • Investigating the impact of Nerfin-1 loss on cell competition dynamics.
  • Examining the function of INSM1 in mammalian cells.

Main Results:

  • Nerfin-1 identified as a transcriptional repressor that binds to the TEA domain of Sd, inhibiting the Sd-Yki complex.
  • Ectopic Nerfin-1 expression leads to reduced tissue growth in an Sd-dependent manner.
  • Loss of Nerfin-1 enhances winner cell elimination during cell competition.
  • Mammalian INSM1 demonstrates a conserved role in repressing TEAD-YAP complex activity.

Conclusions:

  • Nerfin-1 acts as a novel antagonist of the Hippo pathway's transcriptional output by inhibiting the Sd-Yki complex.
  • Nerfin-1 plays a role in regulating tissue growth and cell competition.
  • INSM1, the mammalian ortholog, suggests a conserved mechanism for controlling YAP activity, with implications for cancer and regenerative medicine.
Keywords:
D. melanogasterHippo signalingcell competitiondevelopmental biologyhumanregenerative medicinestem cellstranscription factors

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