An alternatively spliced zebrafish jnk1a transcript has an essential and non-redundant role in development of the first heart field derived proximal ventricular chamber.

Abstract

Alternative splicing is a ubiquitous mechanism for producing different mRNA species from a single gene, resulting in proteomic diversity. Despite potential for regulating embryogenesis, its developmental role remains under-investigated. The Jun kinase (Jnk) genes, considered downstream effectors of the non-canonical Wnt planar cell polarity pathway, utilise extensive and evolutionarily-conserved alternative splicing. Although many PCP members are associated with heart malformation, the role of Jnk genes in cardiac development, and specifically which alternatively spliced transcripts orchestrate these processes, remain unknown. In this study we exploit the jnk1 duplication and subspecialisation found in zebrafish to reveal an essential and non-redundant requirement for jnk1a in cardiac development. We characterise alternatively spliced jnk1a/jnk1b transcripts and demonstrate that hypoplasia of the proximal ventricular component, which corresponds to human hypoplastic left ventricle, can only be rescued by the jnk1a Ex7 Lg transcript. These studies highlight the importance of Jnk signalling and alternative splicing in heart development