No abstract

15The notochord is an embryonic tissue that acts as a precursor to the spine. It is composed of 16 outer sheath cells and inner vacuolated cells. Together they ensure the ability of the notochord 17 to act as a hydrostatic skeleton until ossification begins. To date, there is still a paucity in our 18 understanding of how the notochord cell types are specified and the molecular players 19 controlling both their formation and maintenance remain poorly understood. Here we report 20 that desmogon, a desmosomal cadherin, is essential for proper vacuolated cell shape and 21 therefore correct notochord morphology. We trace desmogon+ precursors and uncover an 22 early developmental heterogeneity that dictates the balance of vacuolated and sheath cell 23 formation. We demonstrate that the growth of vacuolated cells occurs asynchronously and 24 reveal the presence of distinct injury sensing mechanisms in the notochord. Additionally, using 25 a small-scale F0 CRISPR screen we implicate uncharacterized genes in notochordal integrity. 26 93 6 Results 94 95 desmogon is a fish-specific desmosomal cadherin expressed in the notochord 96