期刊
BIOLOGY OPEN
卷 5, 期 3, 页码 359-366出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.016295
关键词
Pelvic fin; Development; TALENs; Hindlimb; Tbx4
类别
资金
- National Health and Medical Research Council (NHMRC) [GNT1034816]
- NHMRC
- Australian Research Council (ARC)
- Macquarie University
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.
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