Genetic basis of hindlimb loss in a naturally occurring vertebrate model
Details
Publication Year 2016-02-18, Volume 5, Issue #3, Page 359-66
Journal Title
Biol Open
Publication Type
Journal Article
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.
Publisher
COB
WEHI Research Division(s)
Development And Cancer
PubMed ID
26892237
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2016-03-15 03:47:42
Last Modified: 2016-05-09 12:42:14
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