Identification and characterisation of the developmental expression pattern of tbx5b, a novel tbx5 gene in zebrafish

Abstract

Tbx5 is a T-box transcription factor that has been characterised in most vertebrate lineages and is widely expressed during the development of various embryonic structures, including the heart, the eyes and the anterior set of paired appendages (tetrapod forelimbs and fish pectoral fins). Mutations in TBX5 cause Holt–Oram syndrome, an autosomal dominant human “heart-hand” condition characterised by upper limb and heart malformations. In zebrafish, embryos with compromised tbx5 function show a complete absence of pectoral fins, whereas heart and eye development are not so highly disturbed. Here, we identify a new tbx5 gene in zebrafish that we have called tbx5b. This duplicate gene is present in all teleost genomes whose sequence is available, suggesting it resulted from the teleost-specific genome duplication event that took place during fish evolution. We show that tbx5b has lost the characteristic forelimb/pectoral fin expression of Tbx5 genes but has retained the eye and heart expression, partially overlapping with that of its paralogue, now referred to as tbx5a. Functional redundancy of tbx5a and tbx5b in the eye and heart would therefore explain the mild phenotypes observed during development of these organs in fish embryos with compromised tbx5a function.