The roles of inter-tissue adhesion in development and morphological evolution

Abstract

The study of how neighboring tissues physically interact with each other, inter-tissue adhesion, is an emerging field at the interface of cell biology, biophysics and developmental biology. Inter-tissue adhesion can be mediated by either cell-extracellular matrix adhesion or cell-cell adhesion, and both the mechanisms and consequences of inter-tissue adhesion have been studied in vivo in numerous vertebrate and invertebrate species. In this Review, we discuss recent progress in understanding the many functions of inter-tissue adhesion in development and evolution. Inter-tissue adhesion can couple the motion of adjacent tissues, be the source of mechanical resistance that constrains morphogenesis, and transmit tension required for normal development. Tissue-tissue adhesion can also create mechanical instability that leads to tissue folding or looping. Transient inter-tissue adhesion can facilitate tissue invasion, and weak tissue adhesion can generate friction that shapes and positions tissues within the embryo. Lastly, we review studies that reveal how inter-tissue adhesion contributes to the diversification of animal morphologies.

Keywords: Adhesion; Cadherin; Extracellular matrix; Integrin; Morphogenesis.

Fig. 1.

Coordinating and resisting tissue motion: two opposing roles of inter-tissue adhesion. (A) A reaction–diffusion model predicts that different diffusion rates of activators and inhibitors create the periodic pattern and size of the developing feather buds in chicken. (B) Illustration of periodic feather bud patterning on the dorsal epidermis of the developing chicken. (C) At the beginning of chicken feather bud development, epidermal cells (top layer of cells) secrete FGF20, which attracts dermal cells (dark purple). Simultaneously, the dermal cells aggregate, leading to bunching of the overlying epidermal cells, causing β-catenin (β-cat) to move to the nucleus of epidermal cells and activate expression of BMP2 and FGF20. This pathway of chemical signals (BMP2 and FGF20) and mechanical signals (dermal cells) functions to create a periodic pattern similar to that created by the reaction–diffusion model with the addition of inter-tissue adhesion-based mechanics. (D) During zebrafish development, neural tube convergence is resisted by inter-tissue adhesion to the neighboring PSM. NC, notochord. The neural tube and PSM are adhered by a gradient of Fibronectin, which is enriched laterally (dark orange) and is less concentrated medially (light orange). (E) Formation of this dynamic gradient of Fibronectin matrix depends upon shear stress at the interface of the neural tube and PSM, as well as activated Integrin α5β1.

Fig. 2.

Inter-tissue adhesion-generated friction and transient adhesion, and their role in positioning tissues. (A) In the gastrulating zebrafish, the neurectoderm moves to the vegetal pole (VP), and the prechordal plate (PPL) moves to the animal pole (AP). Adhesions between the two tissues are formed by E-cadherin–E-cadherin interactions, which generates friction as the tissues move relative to each other. D, dorsal; V, ventral. (B) Knockdown of E-cadherin results in mislocalization of the neural anlage, which can be visualized by in situ hybridization for otx2. Brackets indicate distance to the anterior edge of the neural anlage. WT, wild type. (C) During mammalian embryo implantation, the blastocyst positions itself using L-selectins that bind to oligosaccharides at the endometrium. MUC-1 is a glycoprotein that prevents binding and is removed just before implantation. Once in position, a strong attachment is made that includes interactions with integrins, trophinin and dystroglycan 1, leading to invasion of the endometrium.

Fig. 3.

Inter-tissue-mediated mechanical instability during development of cortical folds. (A) When two adhered tissues grow at different rates (top), stress is generated, which can be relieved by buckling (bottom). (B) The human cerebral cortex exhibits a complex folding pattern, with gray matter overlaying white matter. (C) Differential growth of the future gray matter compared to the slower growing white matter may contribute to buckling in the developing brain. The white matter is primarily composed of apical radial glia cells (aRGCs) and basal radial glia cells (bRGCs) which produce the neurons that migrate to the future gray matter. The gray matter then expands by neuron maturation.

Fig. 4.

Distribution of tension by inter-tissue adhesion in the elongating C. elegans embryo. (A) C. elegans muscle (yellow) is internally attached to the dorsal-ventral epithelium (DVE; cyan), and the DVE is attached to the lateral epithelium (LE) by adherens junctions (AJs), as illustrated in detail in the insets (B and C). (B) The PAR module (PAR), consisting of PAR-3, PAR-6 and PKC-3, localizes to the lateral boundary of the LE where it helps orient the actin cytoskeleton. (C) When the muscle contacts (step 1), the DVE acts as a ‘middleman’ to transmit tension to the LE. Transmission of tension is accomplished with the help of C. elegans hemidesmosomes (CeHD-like junctions) within the DVE. As the muscle contracts, a GIT-1–PIX-1–PAK-1 complex phosphorylates and matures intermediate filaments (IFs) (step 2). The mature CeHDs in the DVE can then transmit force to the LE through apical AJs (step 3). (D) The muscle and CeHD are linked by a shared ECM. The muscle binds to the shared ECM using integrins, while the CeHD uses LET-805 (LET) at the basal side of the DVE. MUP-4 (MUP) and MUA-3 (MUA) located at the apical side are linked to LET by IFs. GIT, GIT-1; P, phosphorylation; PAK, PAK-1; PIX, PIX-1; VAB, VAB-10.

Fig. 5.

Diversifying anatomical shape and the role of inter-tissue adhesion. (A) There is great diversity among vertebrates in the gut looping patterns and loop size, which form due to differential growth between the gut tube (pictured) and dorsal mesentery (not pictured). Representative loop radii (r) are indicated. (B) During Drosophila pupal wing development (top), the wing adheres to the surrounding cuticle (gray) using the apical ECM protein Dumpy (orange). As the hinge contracts (dark green) tension is generated in the wing (light green). Wing shape of the adult fly (bottom). The pattern of anchorage to the cuticle is hypothesized to contribute to wing shape, as tissue-specific RNAi knockdown of dumpy (purple) in the pupal wing (see top right) leads to predictable deformations to wing shape, as observed by an indentation in the wing (position marked with *). (C) In the scuttle fly, the serosa (purple, extraembryonic tissue) surrounds the entire embryo during late embryogenesis. The spreading of the serosa in the scuttle fly depends upon de-adhesion of the serosa from the yolk. (D) In contrast, fruit flies develop a combined amnion and serosa called the amnioserosa, which remains in contact with the yolk and does not spread to encapsulate the entire embryo. It is hypothesized that secretion of Mmp1 in the scuttle fly, but not the fruit fly, decouples the amnion and serosa and enables spreading of the serosa in the scuttle fly. Dashed lines indicate the position of cross sections.