PUBLICATION
Identifying in vivo genetic dependencies of melanocyte and melanoma development
- Authors
- Perlee, S., Ma, Y., Hunter, M.V., Swanson, J.B., Cruz, N.M., Ming, Z., Xia, J., Lionnet, T., McGrail, M., White, R.M.
- ID
- ZDB-PUB-250830-2
- Date
- 2025
- Source
- eLIFE 13: (Other)
- Registered Authors
- Keywords
- CRISPR-Cas9, genetics, genomics, melanocytes, melanoma, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- CRISPR-Cas Systems
- Melanocytes*/metabolism
- Melanocytes*/physiology
- Melanoma*/genetics
- Melanoma*/pathology
- Microphthalmia-Associated Transcription Factor/genetics
- Microphthalmia-Associated Transcription Factor/metabolism
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 40879132 Full text @ Elife
Citation
Perlee, S., Ma, Y., Hunter, M.V., Swanson, J.B., Cruz, N.M., Ming, Z., Xia, J., Lionnet, T., McGrail, M., White, R.M. (2025) Identifying in vivo genetic dependencies of melanocyte and melanoma development. eLIFE. 13:.
Abstract
The advent of large-scale sequencing in both development and disease has identified large numbers of candidate genes that may be linked to important phenotypes. We have developed a rapid, scalable system for assessing the role of candidate genes using zebrafish. We generated transgenic zebrafish in which Cas9 was knocked in to the endogenous mitfa locus, a master transcription factor of the melanocyte lineage. The main advantage of this system compared to existing techniques is maintenance of endogenous regulatory elements. We used this system to identify both cell-autonomous and non-cell-autonomous regulators of normal melanocyte development. We then applied this to the melanoma setting to demonstrate that loss of genes required for melanocyte survival can paradoxically promote more aggressive phenotypes, highlighting that in vitro screens can mask in vivo phenotypes. Our genetic approach offers a versatile tool for exploring developmental processes and disease mechanisms that can readily be applied to other cell lineages.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping