Diverse roles for axon guidance pathways in adult tissue architecture and function

Abstract

Abstract Classical axon guidance ligands and their neuronal receptors were first identified due to their fundamental roles in regulating connectivity in the developing nervous system. Since their initial discovery, it has become clear that these signaling molecules play important roles in the development of a broad array of tissue and organ systems across phylogeny. In addition to these diverse developmental roles, there is a growing appreciation that guidance signaling pathways have important functions in adult organisms, including the regulation of tissue integrity and homeostasis. These roles in adult organisms include both tissue‐intrinsic activities of guidance molecules, as well as systemic effects on tissue maintenance and function mediated by the nervous and vascular systems. While many of these adult functions depend on mechanisms that mirror developmental activities, such as regulating adhesion and cell motility, there are also examples of adult roles that may reflect signaling activities that are distinct from known developmental mechanisms, including the contributions of guidance signaling pathways to lineage commitment in the intestinal epithelium and bone remodeling in vertebrates. In this review, we highlight studies of guidance receptors and their ligands in adult tissues outside of the nervous system, focusing on in vivo experimental contexts. Together, these studies lay the groundwork for future investigation into the conserved and tissue‐specific mechanisms of guidance receptor signaling in adult tissues. Key Points Axon guidance ligand and receptor expression often persist into adulthood in neuronal and non‐neuronal tissues alike. Recent work in genetic model organisms highlights the diverse roles of guidance factors in adult tissues. Guidance factors are required intrinsically in a variety of adult tissues but can also regulate tissue function indirectly via functions in the nervous and vascular systems. Studies outside of the nervous system are likely to enhance our understanding of these diverse siganling molecules and could suggest novel signaling modalities in the nervous system.

Keywords

• axon guidance
• homeostasis
• blood‐brain barrier
• mammary gland
• pancreas
• bone