To adhere or not to adhere: the role of Cadherins in neural crest development

Abstract

The modulation of cell adhesion is fundamental to the morphogenesis that accompanies proper embryonic development. Cadherins are a large family of calcium-dependent cell adhesion molecules whose spatial and temporal expression is critical to the formation of the neural crest, a unique, multipotent cell type that contributes to the patterning of the vertebrate body plan. Neural crest cells arise from the embryonic ectoderm through inductive interactions and reside in the dorsal aspect of the neural tube. These cells under go an epithelial-to-mesenchymal transition and migrate to precise destinations in the embryo, where they go on to differentiate into such diverse structures as melanocytes, elements of the peripheral nervous system and the craniofacial skeleton. Distinct cadherins are expressed during the induction, migration and differentiation of the neural crest. With the advent of genomic sequencing, assembly and annotation for various model organisms, it has become possible to elucidate the molecular mechanisms underlying cadherin expression, and how these cadherins function, during neural crest development. This review explores the known roles of cadherins and details, where relevant, how different cadherins are regulated during the formation of the neural crest.

Figure 1

Domain structure of various cadherin sub-groups. Five cadherin sub-groups can be described in the Cadherin family of cell adhesion molecules. All cadherins possess the ability to bind calcium ions and contain a variable number of common extracellular (EC) domains. Most cadherin sub-groups are defined as single-pass transmembrane proteins possessing one intracellular domain capable of binding different proteins (catenins, kinases), with the exception of the atypical cadherins that are membrance-anchored. Cadherin-like (or -related) proteins, however, span the plasma membrane multiple times and share homology with G protein-coupled receptors.

Figure 2

Cadherin expression during the formation of the neural crest in the avian embryo. Prior to neurulation, E-cadherin (yellow) is expressed throughout the developing embryonic ectoderm. The neural plate is later defined by the acquisition of N-cadherin (blue) and the loss of E-cadherin, which is still maintained in the non-neural ectoderm or future epidermis. During neurulation, N-cadherin expression persists in the invaginating neural plate, while cadherin-6B (green) comes on in the neural folds of the embryo, delineating the future premigratory neural crest cell domain in the dorsal neural tube. Cadherin-6B and N-cadherin are downregulated as neural crest cells undergo EMT, and migratory neural crest cells instead express cadherin-7 (red) as they migrate along stereotypical pathways to their final destinations. During neural crest cell differentiation, N-cadherin expression is detected in the dorsal root ganglia (DRG). Pink cells along the dorsolateral pathway in the bottom panel of the figure indicate migratory neural crest cells expressing multiple cadherins. Structural derivatives of the dorsolateral and dorsoventral pathways are indicated in boxes.