Genetic basis of hindlimb loss in a naturally occurring vertebrate model

Biology Open

Peter D. Currie¹  Garth A. Nicholson²  Benjamin Heng²  Gilles J. Guillemin²  Claire Winnick²  Nicholas J. Cole²  Andrew P. Badrock²  Emily K. Don²  Daniel Hesselson³  Thomas E. Hall⁴  Karen Doggett⁵  Tanya A. de Jong-Curtain⁵  Joan K. Heath⁵ 

[1] Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia;Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales 2109, Australia;Garvan Institute of Medical Research, Diabetes and Metabolism Division, Sydney, New South Wales 2010, Australia;Institute for Molecular Bioscience, University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia;Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia;

关键词: Pelvic fin;    Development;    TALENs;    Hindlimb;    Tbx4;   

DOI  :  10.1242/bio.016295

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown