Mechanisms of convergence and extension by cell intercalation

Abstract

The cells of many embryonic tissues actively narrow in one dimension (convergence) and lengthen in the perpendicular dimension (extension). Convergence and extension are ubiquitous and important tissue movements in metazoan morphogenesis. In vertebrates, the dorsal axial and paraxial mesodermal tissues, the notochordal and somitic mesoderm, converge and extend. In amphibians as well as a number of other organisms where these movements appear, they occur by mediolateral cell intercalation, the rearrangement of cells along the mediolateral axis to produce an array that is narrower in this axis and longer in the anteroposterior axis. In amphibians, mesodermal cell intercalation is driven by bipolar, mediolaterally directed protrusive activity, which appears to exert traction on adjacent cells and pulls the cells between one another. In addition, the notochordal^somitic boundary functions in convergence and extension bỳ capturing' notochordal cells as they contact the boundary, thus elongating the boundary. The prospective neural tissue also actively converges and extends parallel with the mesoderm. In contrast to the mesoderm, cell intercalation in the neural plate normally occurs by monopolar protrusive activity directed medially, towards the midline notoplate^£oor-plate region. In contrast, the notoplate^£oor-plate region appears to converge and extend by adhering to and being towed by or perhaps migrating on the underlying notochord. Converging and extending mesoderm sti¡ens by a factor of three or four and exerts up to 0.6 m N force. Therefore, active, force-producing convergent extension, the mechanism of cell intercalation, requires a mechanism to actively pull cells between one another while maintaining a tissue sti¡ness su¤cient to push with a substantial force. Based on the evidence thus far, a cell^cell traction model of intercalation is described. The essential elements of such a morphogenic machine appear to be (i) bipolar, mediolaterally orientated or monopolar, medially directed protrusive activity; (ii) this protrusive activity results in mediolaterally orientated or medially directed traction of cells on one another; (iii) tractive protrusions are con¢ned to the ends of the cells; (iv) a mechanically stable cell cortex over the bulk of the cell body which serves as a movable substratum for the orientated or directed cell traction. The implications of this model for cell adhesion, regulation of cell motility and cell polarity, and cell and tissue biomechanics are discussed.

Xenopus fibrillin is expressed in the organizer and is the earliest component of matrix at the developing notochord‐somite boundary

“…The localization of XF protein to the developing notochord-somite boundaries suggests that XF functions in the process of axial convergence and extension driven by cell intercalation, because these boundaries have been implicated in regulating convergence and extension at several levels (Keller et al, 2000). These matrix-containing structures appear and elongate as straight lines of separation of presumptive notochordal and somitic cells at stage 11-11.5, the midgastrula (Shih and Keller, 1992b), and the pattern of boundary formation is reflected in the pattern of induction of cell motile behaviors that drive intercalation and thus dorsal, axial morphogenesis.…”

“…The bulk of this morphogenesis occurs at gastrulation and is largely driven by convergence and extension of the involuting axial and paraxial mesoderm that gives rise to notochord and somites. This convergence and extension is driven by a patterned cell motility in this tissue termed mediolateral intercalation behavior (MIB) (Keller et al, 2000). This tissue exhibits an anisotropic increase in stiffness and generates directed force to drive normal, asymmetric blastopore closure and archenteron elongation at gastrulation (Moore et al, 1995).…”

“…This boundary regulates both cell motility, by inducing presumptive notochordal cells that contact the boundary to transit from a bipolar to a monopolar protrusive state, and the expression of cell fate in the presumptive notochord (Domingo and Keller, 1995). However, the molecular basis underlying regulation of this patterned cell motility, the change in stiffness and force production exhibited by this tissue, and the role of the ECM at the developing notochord-somite boundary, remains unclear (Keller et al, 2000).…”

How cellular movement determines the collective force generated by the Dictyostelium discoideum slug

“…Adhesive forces Detailed modeling of cell adhesion is a major effort in itself, and as a simplification the PO model splits the adhesional force into two components, one tangential to the cell membrane and one normal to the membrane. This is motivated by the idea that cell adhesion may be less resistant to tangential forces and more resistant to normal forces (Keller et al, 2000).…”

Initiation of convergence and extension movements of lateral mesoderm during zebrafish gastrulation

“…Near the end of epiboly, lateral mesodermal cells form tightly packed aggregates that converge using dorsalward translocation of cell groups and extend (Jessen et al, 2002). In Xenopus laevis and in the notochord of the zebrafish, convergence and extension of the mesoderm are driven by the mediolateral intercalation of cells (Keller et al, 2000;Glickman et al, 2003). Ectodermal cells manage a similar morphogenesis while in the apparent configuration of a cellular sheet (Concha and Adams, 1998).…”