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The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals

Nailing Zhang1, Haibo Bai, Karen K David

  • 1Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Developmental Cell
|July 21, 2010
PubMed

Insights

The Merlin/NF2 tumor suppressor and YAP oncoprotein antagonistically regulate organ size. Merlin/NF2 inactivation causes cancer, and YAP activation mediates related pathologies, linking NF2 to Hippo signaling.

Area of Science:

  • Cell biology
  • Molecular biology
  • Oncology

Background:

  • The Hippo signaling pathway is crucial for organ size regulation in mammals.
  • Upstream regulators of the Hippo pathway, particularly in mammals, require further elucidation.
  • Merlin (encoded by NF2) is a tumor suppressor, and YAP is an oncoprotein with roles in growth regulation.

Purpose of the Study:

  • To investigate the roles of Merlin/NF2 and YAP in mammalian liver development.
  • To determine the functional relationship between Merlin/NF2 and the Hippo signaling pathway.
  • To explore the involvement of YAP activation in pathologies associated with Neurofibromatosis 2.

Main Methods:

  • Utilized conditional knockout mice to study gene function in vivo.
  • Generated mice with targeted inactivation of Yap and Nf2.
  • Assessed the impact of these genetic modifications on liver development and tumor formation.

Main Results:

  • Inactivation of Yap resulted in the loss of hepatocytes and biliary epithelial cells.
  • Inactivation of Nf2 led to hepatocellular carcinoma and bile duct hamartoma.
  • Heterozygous deletion of Yap significantly suppressed Nf2-deficient phenotypes, indicating YAP as a key effector of Merlin/NF2.

Conclusions:

  • Merlin/NF2 and YAP function antagonistically in regulating liver development.
  • Merlin/NF2 is linked to the mammalian Hippo signaling pathway.
  • YAP activation is implicated as a mediator of pathologies relevant to Neurofibromatosis 2.

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