PLOS Genetics study implicates Yap1 in vertebral development and kyphoscoliosis prevention in zebrafish

A study published in PLOS Genetics by Victoria C. Williams-Ward, Kees Wanders, Simon M. Hughes, and colleagues describes the role of Yap1 — a transcriptional co-activator and component of the Hippo signalling pathway — in vertebral development and the prevention of kyphoscoliosis in zebrafish.

The researchers report transient expression of yap1 mRNA in precursor cells of muscle and notochord during zebrafish development, alongside expression of the related gene wwtr1. Loss of Yap1 function in the model leads to kyphoscoliosis — an abnormal spinal curvature — implicating the gene in the mechanical feedback interactions between the neuromuscular and skeletal systems that are thought to be important in spine morphogenesis.

Scoliosis affects an estimated 2–3% of people and frequently develops during or after adolescence. Mechanosignalling — the process by which cells sense and respond to mechanical forces — is increasingly recognised as a significant contributor to spinal curvature disorders, though the molecular details have remained incompletely defined. The zebrafish model is well established as a system for studying vertebrate spine development given the optical accessibility and genetic tractability of the organism.

This peer-reviewed article complements but is distinct from a concurrent preprint (also in this batch) applying transcriptomic analysis to adolescent idiopathic scoliosis GWAS loci in humans. Together, the two papers reflect growing momentum in scoliosis genetics research.