Notochord morphogenesis as a mechanical driver of embryo axis elongation

Abstract

Early on in development, embryos undergo a dramatic change in shape in order to transform from a collection of cells into a functioning organism with a specialised body morphology. A key step in this process is the elongation of the head-to-tail, or anterior-posterior (AP) embryonic axis. For axis elongation to occur, multiple tissues must deform concomitantly, often elongating through a combination of convergence and extension and/or volumetric growth. As tissues deform, they exert force on their neighbouring tissues. How the force generated by the morphogenesis of one tissue impacts that of other axial tissues to achieve an elongated embryo axis is currently not well understood. The notochord, a rod-shaped tissue running through the middle of all vertebrate embryos, is a key candidate for driving this process. Cells in the notochord undergo an expansion that is constrained by a stiff sheath of extracellular matrix that increases the internal pressure in the notochord, allowing it to straighten and elongate. The notochord is flanked on either side by the somitic compartment made up of developing somites in the segmented region of the axis and presomitic mesoderm in the posterior. Therefore, it is appropriately positioned to play a role in mechanically elongating the somitic compartment. In this PhD thesis I characterise axis elongation and notochord morphogenesis in the developing zebrafish embryo and generate hypotheses on the mechanical role of the notochord in extending the embryo axis. Using a spatially and temporally specific multi-photon ablation technique, I investigate the mechanical role of the notochord in elongating the somitic compartment. I show that anterior notochord cell expansion generates a force that displaces notochord cells posteriorly relative to adjacent axial tissues and contributes to the elongation of segmented tissue during post-tailbud stages of development. Crucially, unexpanded cells derived from progenitors at the posterior end of the notochord provide resistance to anterior notochord cell expansion, allowing for force generation along the notochord. Therefore, notochord cell expansion beginning in the anterior, and addition of cells to the posterior notochord, act as temporally coordinated morphogenetic events that shape the zebrafish embryo AP axis.