ZFIN ID: ZDB-PUB-190828-3
Somatic Mutations of lats2 Cause Peripheral Nerve Sheath Tumors in Zebrafish
Brandt, Z.J., North, P.N., Link, B.A.
Date: 2019
Source: Cells   8(9): (Journal)
Registered Authors: Link, Brian
Keywords: Hippo, Lats2, Taz, Yap, peripheral nerve sheath tumor, schwannoma, zebrafish
MeSH Terms:
  • Animals
  • CRISPR-Cas Systems
  • Cell Proliferation
  • Gene Editing
  • Mutation*
  • Neoplasms, Experimental/genetics
  • Neoplasms, Experimental/metabolism
  • Neoplasms, Experimental/pathology*
  • Nerve Sheath Neoplasms/genetics
  • Nerve Sheath Neoplasms/metabolism
  • Nerve Sheath Neoplasms/pathology*
  • Protein-Serine-Threonine Kinases/genetics*
  • Protein-Serine-Threonine Kinases/metabolism
  • Signal Transduction
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/metabolism
PubMed: 31450674 Full text @ Cells
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ABSTRACT
The cellular signaling pathways underlying peripheral nerve sheath tumor (PNST) formation are poorly understood. Hippo signaling has been recently implicated in the biology of various cancers, and is thought to function downstream of mutations in the known PNST driver, NF2. Utilizing CRISPR-Cas9 gene editing, we targeted the canonical Hippo signaling kinase Lats2. We show that, while germline deletion leads to early lethality, targeted somatic mutations of zebrafish lats2 leads to peripheral nerve sheath tumor formation. These peripheral nerve sheath tumors exhibit high levels of Hippo effectors Yap and Taz, suggesting that dysregulation of these transcriptional co-factors drives PNST formation in this model. These data indicate that somatic lats2 deletion in zebrafish can serve as a powerful experimental platform to probe the mechanisms of PNST formation and progression.
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