PUBLICATION
Genetic basis of hindlimb loss in a naturally occurring vertebrate model
- Authors
- Don, E.K., de Jong-Curtain, T.A., Doggett, K., Hall, T.E., Heng, B., Badrock, A.P., Winnick, C., Nicholson, G.A., Guillemin, G.J., Currie, P.D., Hesselson, D., Heath, J.K., Cole, N.J.
- ID
- ZDB-PUB-160220-10
- Date
- 2016
- Source
- Biology Open 5(3): 359-66 (Journal)
- Registered Authors
- Badrock, Andrew P., Cole, Nicholas, Currie, Peter D., Doggett, Karen, Don, Emily, Hall, Thomas, Heath, Joan K., Hesselson, Daniel
- Keywords
- Development, Hindlimb, Pelvic fin, TALENs, Tbx4
- MeSH Terms
- none
- PubMed
- 26892237 Full text @ Biol. Open
Citation
Don, E.K., de Jong-Curtain, T.A., Doggett, K., Hall, T.E., Heng, B., Badrock, A.P., Winnick, C., Nicholson, G.A., Guillemin, G.J., Currie, P.D., Hesselson, D., Heath, J.K., Cole, N.J. (2016) Genetic basis of hindlimb loss in a naturally occurring vertebrate model. Biology Open. 5(3):359-66.
Abstract
Here we genetically characterise pelvic finless, a naturally occurring model of hindlimb loss in zebrafish that lacks pelvic fin structures, which are homologous to tetrapod hindlimbs, but displays no other abnormalities. Using a hybrid positional cloning and next generation sequencing approach, we identified mutations in the nuclear localisation signal (NLS) of T-box transcription factor 4 (Tbx4) that impair nuclear localisation of the protein, resulting in altered gene expression patterns during pelvic fin development and the failure of pelvic fin development. Using a TALEN-induced tbx4 knockout allele we confirm that mutations within the Tbx4 NLS (A78V; G79A) are sufficient to disrupt pelvic fin development. By combining histological, genetic, and cellular approaches we show that the hindlimb initiation gene tbx4 has an evolutionarily conserved, essential role in pelvic fin development. In addition, our novel viable model of hindlimb deficiency is likely to facilitate the elucidation of the detailed molecular mechanisms through which Tbx4 functions during pelvic fin and hindlimb development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping