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Somatic Mutations of lats2 Cause Peripheral Nerve Sheath Tumors in Zebrafish

Zachary J Brandt1, Paula N North2, Brian A Link3

  • 1Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Cells
|August 28, 2019
PubMed

Insights

Targeting Lats2 in zebrafish with CRISPR-Cas9 gene editing caused peripheral nerve sheath tumors (PNSTs). This study highlights the Hippo signaling pathway

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Peripheral nerve sheath tumor (PNST) formation mechanisms are not well understood.
  • Hippo signaling is implicated in cancer and may function downstream of NF2 mutations, a known PNST driver.

Purpose of the Study:

  • To investigate the role of the Hippo signaling kinase Lats2 in PNST formation.
  • To establish a zebrafish model for studying PNST development and progression.

Main Methods:

  • CRISPR-Cas9 gene editing was used to target Lats2 in zebrafish.
  • Somatic mutations of Lats2 were induced to study PNST development.

Main Results:

  • Germline deletion of Lats2 resulted in early lethality in zebrafish.
  • Targeted somatic mutations of Lats2 led to the formation of PNSTs.
  • These PNSTs showed elevated levels of Hippo pathway effectors Yap and Taz.

Conclusions:

  • Somatic Lats2 deletion in zebrafish is a viable model for studying PNST formation.
  • Dysregulation of Hippo signaling, specifically Lats2, contributes to PNST development.
  • Yap and Taz appear to be key transcriptional co-factors driving PNSTs in this model.
Keywords:
HippoLats2TazYapperipheral nerve sheath tumorschwannomazebrafish

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