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.
| Language | English |
|---|---|
| Pages | 359-366 |
| Number of pages | 8 |
| Journal | Biology Open |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 15 Mar 2016 |
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Bibliographical note
Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Cite this
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Genetic basis of hindlimb loss in a naturally occurring vertebrate model. / Don, Emily K.; De Jong-Curtain, Tanya A.; Doggett, Karen; Hall, Thomas E.; Heng, Benjamin; Badrock, Andrew P.; Winnick, Claire; Nicholson, Garth A.; Guillemin, Gilles J.; Currie, Peter D.; Hesselson, Daniel; Heath, Joan K.; Cole, Nicholas J.
In: Biology Open, Vol. 5, No. 3, 15.03.2016, p. 359-366.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Genetic basis of hindlimb loss in a naturally occurring vertebrate model
AU - Don,Emily K.
AU - De Jong-Curtain,Tanya A.
AU - Doggett,Karen
AU - Hall,Thomas E.
AU - Heng,Benjamin
AU - Badrock,Andrew P.
AU - Winnick,Claire
AU - Nicholson,Garth A.
AU - Guillemin,Gilles J.
AU - Currie,Peter D.
AU - Hesselson,Daniel
AU - Heath,Joan K.
AU - Cole,Nicholas J.
N1 - Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2016/3/15
Y1 - 2016/3/15
N2 - 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.
AB - 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.
KW - Development
KW - Hindlimb
KW - Pelvic fin
KW - TALENs
KW - Tbx4
UR - http://www.scopus.com/inward/record.url?scp=84978476526&partnerID=8YFLogxK
U2 - 10.1242/bio.016295
DO - 10.1242/bio.016295
M3 - Article
VL - 5
SP - 359
EP - 366
JO - Biology Open
T2 - Biology Open
JF - Biology Open
SN - 2046-6390
IS - 3
ER -