PUBLICATION
Localized heterochrony integrates overgrowth potential of oncogenic clones
- Authors
- Blum, N., Harris, M.P.
- ID
- ZDB-PUB-230110-7
- Date
- 2023
- Source
- Disease models & mechanisms 16(2): (Journal)
- Registered Authors
- Harris, Matthew
- Keywords
- Cartilage condensation, Macrodactyly, Proteus syndrome, Skeleton, Somatic mutation, Zebrafish
- MeSH Terms
-
- Animals
- Clone Cells
- Mosaicism*
- Mutation/genetics
- Phenotype
- Zebrafish*/genetics
- PubMed
- 36621776 Full text @ Dis. Model. Mech.
Citation
Blum, N., Harris, M.P. (2023) Localized heterochrony integrates overgrowth potential of oncogenic clones. Disease models & mechanisms. 16(2):.
Abstract
Somatic mutations occur frequently and can arise during embryogenesis resulting in the formation of a patchwork of mutant clones. Such mosaicism has been implicated in a broad range of developmental anomalies, however their etiology is poorly understood. Patients carrying a common somatic oncogenic mutation in either PIK3CA or AKT1, can present with disproportionally large digits or limbs. How mutant clones, carrying an oncogenic mutation that often drives unchecked proliferation can lead to controlled and coordinated overgrowth is unknown. We use zebrafish to explore the growth dynamics of oncogenic clones during development. In a subset of clones, we observe a local increase in proportion of the fin skeleton closely resembling overgrowth phenotypes in patients. We unravel the cellular and developmental mechanisms of these overgrowths and pinpoint the cell type and timing of clonal expansion. Coordinated overgrowth is associated with rapid clone expansion during early pre-chondrogenic phase of bone development inducing a heterochronic shift that drives the change in bone size. Our study details how development integrates and translates growth potential of oncogenic clones, thereby shaping the phenotypic consequences of somatic mutations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping