The role of cell adhesion molecules in visual circuit formation: From neurite outgrowth to maps and synaptic specificity

Abstract

The formation of visual circuitry is a multistep process that involves cell–cell interactions based on a range of molecular mechanisms. The correct implementation of individual events, including axon outgrowth and guidance, the formation of the topographic map, or the synaptic targeting of specific cellular subtypes, are prerequisites for a fully functional visual system that is able to appropriately process the information captured by the eyes. Cell adhesion molecules (CAMs) with their adhesive properties and their high functional diversity have been identified as key actors in several of these fundamental processes. Because of their growth‐promoting properties, CAMs play an important role in neuritogenesis. Furthermore, they are necessary to control additional neurite development, regulating dendritic spacing and axon pathfinding. Finally, trans‐synaptic interactions of CAMs ensure cell type‐specific connectivity as a basis for the establishment of circuits processing distinct visual features. Recent discoveries implicating CAMs in novel mechanisms have led to a better general understanding of neural circuit formation, but also revealed an increasing complexity of their function. This review aims at describing the different levels of action for CAMs to shape neural connectivity, with a special focus on the visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 569–583, 2015

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse

“…These processes require discrete cell adhesion molecules (CAMs) to establish and maintain the specific interactions, and T-box TFs have been shown to regulate specific CAMs in these processes and tumor metastasis (Yamamoto et al, 1998, Hasson et al, 2010, Rodriguez et al, 2008, Sun et al, 2014). During visual system development, CAMs are indispensable in neurite outgrowth, axon pathfinding, dendritic spacing, RGC laminar targeting, and trans-synaptic interactions, which are important components in establishing functional retinal circuits (Missaire and Hindges, 2015, Yamagata and Sanes, 2012, Osterhout et al, 2011, Sanes and Zipursky, 2010, Zipursky and Sanes, 2010). Our evidence indicates that Tbr1 is an upstream regulator of both symmetrical and asymmetrical Tbr1+ RGCs and that Tbr1 is essential for Jam2 expression.…”

Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

“…The Chemoaffinity hypothesis, formalized by Roger Sperry ( Sperry, 1963 ), suggests that growing neurons must carry individual identification tags that allow the recognition between synaptic partners. Although many cell-type specific recognition molecules essential for neural circuit assembly have been identified in recent years (reviewed in Missaire and Hindges, 2015 ; Yogev and Shen, 2014 ), the precise developmental context in which these molecular tags control cell recognition and specify synaptic identity remain largely elusive.…”

SynCAMs – From axon guidance to neurodevelopmental disorders

“…Thus, not surprisingly, IgSF CAMs were found at synapses and many of them were found to interfere with synaptogenesis when downregulated. For instance, synaptic targeting in the retina was affected in the absence of Contactins, DSCAM, and Sidekicks (Yamagata and Sanes, 2012; reviewed by Missaire and Hindges, 2015). Contactins were also shown to interfere with synapse formation in the cerebellum (reviewed in Stoeckli, 2010).…”