The desmosomal cadherin Desmogon is necessary for the structural integrity of the Medaka notochord

The notochord is an embryonic tissue that acts as a precursor to the spine. It is composed of outer sheath cells and inner vacuolated cells. Together they ensure the ability of the notochord to act as a hydrostatic skeleton until ossification begins. To date, there is still a paucity in our understanding of how the notochord cell types are specified and the molecular players controlling both their formation and maintenance remain poorly understood. Here we report that desmogon , a desmosomal cadherin, is essential for proper vacuolated cell shape and therefore correct notochord morphology. We trace desmogon+ precursors and uncover an early developmental heterogeneity that dictates the balance of vacuolated and sheath cell formation. We demonstrate that the growth of vacuolated cells occurs asynchronously and reveal the presence of distinct injury sensing mechanisms in the notochord. Additionally, using a small-scale F0 CRISPR screen we implicate uncharacterized genes in notochordal integrity.