Notochord morphogenesis in Xenopus laevis: simulation of cell behavior underlying tissue convergence and extension

ABSTRACT Cell intercalation and cell shape changes drive notochord morphogenesis in the African frog, Xenopus laevis. Experimental observations show that cells elongate mediolaterally and intercalate between one another, causing the notochord to lengthen and narrow. Descriptive observations provide few clues as to the mechanisms that coordinate and drive these cell movements. It is possible that a few rules governing cell behavior could orchestrate the shaping of the entire tissue. We test this hypothesis by constructing a computer model of the tissue to investigate how rules governing cell motility and cell-cell interactions can account for the major features of notochord morphogenesis. These rules are drawn from the literature on in vitro cell studies and experimental observations of notochord cell behavior. The following types of motility rules are investigated: (1) refractory tissue boundaries that inhibit cell motility, (2) statistical persistence of motion, (3) contact inhibition of protrusion between cells, and (4) polarized and nonpolarized protrusive activity. We show that only the combination of refractory boundaries, contact inhibition and polarized protrusive activity reproduces normal notochord development. Guided by these rules, cells spontaneously align into a parallel array of elongating cells. Self alignment optimizes the geometric conditions for polarized protrusive activity by progressively minimizing contact inhibition between cells. Cell polarization, initiated at refractory tissue boundaries, spreads along successive cell rows into the tissue interior as cells restrict and constrain their neighbors’ directional bias. The model demonstrates that several experimentally observed intrinsic cell behaviors, operating simultaneously, may underlie the generation of coordinated cell movements within the developing notochord.