The tissue mechanics of vertebrate body elongation and segmentation

Abstract

England's King Richard III, whose skeleton was recently discovered lying ignobly beneath a parking lot, suffered from a lateral curvature of his spinal column called scoliosis. We now know that his scoliosis was not caused by 'imbalanced bodily humors', rather vertebral defects arise from defects in embryonic elongation and segmentation. This review highlights recent advances in our understanding of post-gastrulation biomechanics of the posteriorly advancing tailbud and somite morphogenesis. These processes are beginning to be deciphered from the level of gene networks to a cross-scale physical model incorporating cellular mechanics, the extracellular matrix, and tissue fluidity.

Figure 1. Tissue mechanics during zebrafish trunk elongation

(A) Cell motion in the tailbud can be quantified using metrics from fluid mechanics and thus described as cell flow. The first major transition in cell flow occurs as mesodermal progenitors migrate from the Dorsal Medial Zone into the Progenitor Zone (PZ) where they begin to express mesoderm specific transcription factors such as tbx16, tbx6 (in the mouse and chick) /tbx6l (in zebrafish) and mesogenin. The second transition in tissue fluidity occurs as Progenitor Zone cells assimilate into the Presomitic Mesoderm (PSM). (B) During assembly of the PSM, rapidly moving PZ cells (green; time point 1), reduce their instantaneous velocities, (time point 2). This transition coincides with the assembly of a Fibronectin matrix on the surface of the paraxial mesoderm, but the Fibronectin matrix is not necessary for the transition in cell motion. The Fibronectin matrix is required for normal elongation of the bilateral columns of paraxial mesoderm. In addition, the Fibronectin matrix mechanically couples the paraxial mesoderm and elongating notochord.

Figure 2. Somite morphogenesis

The S0 is the region in the anterior presomitic mesoderm that will form the next somites. The SI is the most recently formed somite and the SII is the preceding somite. In the presomitic mesoderm, the segmentation clock creates a segmental prepattern and stripes of expression of the transcription factor Mesp, which in turn sets up stripes of EphA4 and EphrinB2 expression flanking the somite boundary. Eph/Ephrin signaling activates Integrin α5 which then initiates assembly of Fibronectin matrix along the somite boundary. Integrin αV, Rap1, Ena/Vasp and FAK also promote Fibronectin matrix assembly. Upon initiation of boundary formation, the somite boundary cells undergo a mesenchymal to epithelial transition. This transition is inhibited by Cdc42 in the presomitic mesoderm and promoted by Rac1 in the forming somite. Eph/Ephrin signaling and Integrin α5/Fibronectin also promote the mesenchymal to epithelial transition.