Cellular, molecular, and biophysical control of epithelial cell intercalation

Abstract

Convergent extension is a conserved mechanism for elongating tissues. In the Drosophila embryo, convergent extension is driven by planar polarized cell intercalation and is a paradigm for understanding the cellular, molecular, and biophysical mechanisms that establish tissue structure. Studies of convergent extension in Drosophila have provided key insights into the force-generating molecules that promote convergent extension in epithelial tissues, as well as the global systems of spatial information that systematically organize these cell behaviors. A general framework has emerged in which asymmetrically localized proteins involved in cytoskeletal tension and cell adhesion direct oriented cell movements, and spatial signals provided by the Toll, Tartan, and Teneurin receptor families break planar symmetry to establish and coordinate planar cell polarity throughout the tissue. In this chapter, we describe the cellular, molecular, and biophysical mechanisms that regulate cell intercalation in the Drosophila embryo, and discuss how research in this system has revealed conserved biological principles that control the organization of multicellular tissues and animal body plans.

Keywords: Biomechanics; Cell intercalation; Compartment boundary; Convergent extension; Drosophila; Germband extension; Myosin; Planar polarity; Teneurin; Toll receptors.

Figure 1.. Cell rearrangements during Drosophila germband extension.

(A) Convergent extension in the germband ectoderm (gray) elongates the anterior-posterior (AP) body axis. (B) T1 processes occur through the contraction of a single vertical cell interface. (C) Multicellular rosettes form through the contraction of 2 interfaces (for a 5-cell rosette), 3 interfaces (for a 6-cell rosette), or 4 or more interfaces (for rosettes containing 7 or more cells). (D) The germband ectoderm is a simple columnar epithelium. (E) An en face view of showing one hexagonal cell and its neighbors. (F) Cross-sectional view showing different cellular domains along the apical-basal axis.

Figure 2.. Planar polarity in the Drosophila germband.

(A) Vertical cell interfaces in the germband display increased localization or activity of proteins involved in promoting cortical tension, adherens junction turnover, and endocytosis. (B) Horizontal interfaces are enriched for proteins involved in cell adhesion. (C) Rho-kinase activity at vertical interfaces directs multiple aspects of planar polarity.

Figure 3.. Receptor systems mediating planar polarity in the germband.

(A) Schematics of Toll receptors, Tartan, and Ten-m (not to scale). (B) Toll-2, Toll-6, and Toll-8 are expressed in staggered striped patterns in the germband. C) tartan (purple) is expressed in stripes and Ten-m protein (green) is enriched at the stripe borders. (D) The germband is organized into double-parasegment units, each made up of seven or eight columns of cells. Even parasegments (cells 1–4), odd parasegments (cells 5–8). Wingless-expressing cells are shown in gray. (E) Toll receptor expression within the double-parasegment unit. (F) Tartan expression and Ten-m localization within the double-parasegment unit. Ten-m is enriched at compartment boundaries and is absent from the membrane in Tartan-positive cells.

Figure 4.. Models for how striped Toll receptors generate planar polarity.

(A) In a heterotypic activation model, trans interactions between cells expressing different Toll receptors (purple and orange) in adjacent stripes could stabilize Toll receptors at vertical interfaces. (B) In a homotypic inactivation model, trans interactions between cells expressing the same Toll receptor type could destabilize Toll receptors at horizontal interfaces. (C) In a homotypic activation model, trans interactions between cells expressing the same Toll receptor type could stabilize receptors at horizontal interfaces. (D) In a partner patterning model, a patterned Toll receptor (purple) and an unpatterned interaction partner (green) could undergo inhibitory cis interactions and stabilizing trans interactions, promoting the enrichment of the partner at vertical interfaces along the Toll stripe border.

Figure 5.. Region-specific cell behaviors in the Drosophila embryo.

(A) Embryo schematic showing the germband ectoderm (blue) and mesoderm (yellow). (B) GPCR signaling through the Gα alpha subunit and RhoGEF2 activates myosin in the medial (apical) cellular domain. GPCR signaling through the Gβ/Gγ subunits and the RhoGEF Dp114/Cysts recruits myosin to adherens junctions in the ectoderm to promote cell intercalation. (C) Schematic of intercalating cells in the ectoderm. (D) Schematic of apically constricting cells in the mesoderm.