Genetic basis of hindlimb loss in a naturally occurring vertebrate model

Biology Open
Emily K DonNicholas J Cole

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.

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Citations

Dec 21, 2016·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Aditya SaxenaKimberly L Cooper
Feb 7, 2017·Nature Reviews. Genetics·Florence PetitNadav Ahituv
Jan 23, 2020·European Journal of Human Genetics : EJHG·Prajnya RanganathAshwin Dalal
Dec 16, 2016·Nature·Qiang LinByrappa Venkatesh
May 18, 2019·Science China. Life Sciences·Chao BianQiong Shi
Oct 1, 2019·Zoological Science·Yuuta MoriyamaMikiko Tanaka
Jun 28, 2019·Developmental Biology·Elena F BoerMichael D Shapiro

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Datasets Mentioned

BETA
ENSOANG00000011525

Methods Mentioned

BETA
PCR
in vitro transcription
dissection
transfection

Software Mentioned

SOAPaligner
BWA
Geneious
GATK
Leica application suite
TAL Effector - Nucleotide Targeter
SOAPsnp
Illumina basecalling

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