PUBLICATION
Somatic Mutations of lats2 Cause Peripheral Nerve Sheath Tumors in Zebrafish
- Authors
- Brandt, Z.J., North, P.N., Link, B.A.
- ID
- ZDB-PUB-190828-3
- 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
Citation
Brandt, Z.J., North, P.N., Link, B.A. (2019) Somatic Mutations of lats2 Cause Peripheral Nerve Sheath Tumors in Zebrafish. Cells. 8(9).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping