Mechanisms of convergence and extension by cell intercalation

The cells of many embryonic tissues actively narrow in one dimension (conve rgence) and lengthen in the perpendicular dimension (extension). Convergenc e and extension ae ubiquitous and important tissue movements in metazoan mo rphogenesis. In vertebrates, the dorsal axial and paraxial mesodermal tissu es, the notochordal and somitic mesoderm, converge and extend. In amphibian s as well as a number of other organisms where these movements appear, they occur by mediolateral cell intercalation, the rearrangement of cell salon the mediolateral axis to produce an array that is narrower in this axis and longer in the anteroposterior axis. In amphibians, mesodermal cell interca lation is driven by bipolar, mediolaterally directed protrusive activity, w hich appears to exert traction on adjacent cells and pulls the cells betwee n one another. In addition, the notochordal-somitic boundary functions in c onvergence and extension by 'capturing' notochordal cells as they contact t he boundary, thus elongating the boundary. The prospective neural tissue al so actively converges and extends parallel with the mesoderm. In contrast t o the mesoderm, cell intercalation in the neural plate normally occur by mo nopolar protrusive activity directed medially, towards the midline notoplat e floor-plate region. In contrast, the notoplate-floor-plate region appears to converge and extend by adhering to and being towed by or perhaps migrat ing on the underlying notochord. Converging and extending mesoderm stiffens by a factor of three or four and exerts up to 0.6 mu N force. Therefore, a ctive force-producing convergent extension, the mechanism of cel intercalat ion, requires a mechanism to actively pull cells between one another while maintaining a tissue stiffness sufficient to push with a substantial force. Based on the evidence thus far, a cell-cell traction model of intercalatio n is described. The essential elements of such a a morphogenic machine appe ar to be (i) bipolar, mediolaterally orientated or monopolar, medially dire cted protrusive activity; (ii) this protrusive activity results in mediolat erally oriented or medially directed traction of cells on one another; (iii ) tractive protrusions are confined to th ends of the cells; (iv) a mechani cally stable cell cortex over th bulk of the cell body which serves as a mo vable substratum for the orientated or directed cell traction. The implicat ions of his model for cell adhesion, regulation of cell motility and cell p olarity, and cell and tissue biomechanics are discussed.