PUBLICATION
Characterisation of lmx1b paralogues in zebrafish reveals divergent roles in skeletal, kidney and muscle development
- Authors
- Moss, J.J., Neal, C.R., Kague, E., Lane, J.D., Hammond, C.L.
- ID
- ZDB-PUB-250820-1
- Date
- 2025
- Source
- Biology Open 14: (Journal)
- Registered Authors
- Hammond, Chrissy, Kague, Erika
- Keywords
- Cartilage, Kidney, Lmx1b, Musculoskeletal development, Nail-patella syndrome, Zebrafish
- MeSH Terms
-
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Phenotype
- Animals
- Gene Expression Regulation, Developmental
- Zebrafish*/embryology
- Zebrafish*/genetics
- Nail-Patella Syndrome/genetics
- Transcription Factors*/genetics
- Transcription Factors*/metabolism
- LIM-Homeodomain Proteins*/genetics
- LIM-Homeodomain Proteins*/metabolism
- Muscle Development*/genetics
- Kidney*/embryology
- Kidney*/metabolism
- Muscle, Skeletal*/embryology
- Muscle, Skeletal*/metabolism
- Mutation
- PubMed
- 40829147 Full text @ Biol. Open
Citation
Moss, J.J., Neal, C.R., Kague, E., Lane, J.D., Hammond, C.L. (2025) Characterisation of lmx1b paralogues in zebrafish reveals divergent roles in skeletal, kidney and muscle development. Biology Open. 14:.
Abstract
LMX1B, a LIM-homeodomain family transcription factor, plays critical roles in the development of multiple tissues, including limbs, eyes, kidneys, brain, and spinal cord. Mutations in the human LMX1B gene cause the rare autosomal-dominant disorder Nail-patella syndrome, which affects development of limbs, eyes, brain, and kidneys. In zebrafish, lmx1b has two paralogues: lmx1ba and lmx1bb. While lmx1b morpholino data exists, stable mutants were previously lacking. Here, we describe the characterisation of lmx1b stable mutant lines, with a focus on development of tissues that are affected in Nail-patella syndrome. We demonstrate that the lmx1b paralogues have divergent developmental roles in zebrafish, with lmx1ba affecting skeletal and neuronal development, and lmx1bb affecting renal development. The double mutant, representing loss of both paralogues (lmx1b dKO) showed a stronger phenotype, which included additional defects to trunk muscle patterning, and a failure to fully inflate the notochord leading to a dramatic reduction in body length. Overall, these mutant lines demonstrate the utility of zebrafish for modelling Nail-patella syndrome and describe a previously undescribed role for lmx1b in notochord cell inflation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping