Abstract
Neuronal axons are guided to their target during the development of the brain. Axon guidance allows the formation of intricate neural circuits that control the function of the brain, and thus the behavior. As the axons travel in the brain to find their target, they encounter various axon guidance cues, which interact with the receptors on the tip of the growth cone to permit growth along different signaling pathways. Although many scientists have performed numerous studies on axon guidance signaling pathways, we still have an incomplete understanding of the axon guidance system. Lately, studies on axon guidance have shifted from studying the signal transduction pathways to studying other molecular features of axon guidance, such as the gene expression. These new studies present evidence for different molecular features that broaden our understanding of axon guidance. Hence, in this review we will introduce recent studies that illustrate different molecular features of axon guidance. In particular, we will review literature that demonstrates how axon guidance cues and receptors regulate local translation of axonal genes and how the expression of guidance cues and receptors are regulated both transcriptionally and post-transcriptionally. Moreover, we will highlight the pathological relevance of axon guidance molecules to specific diseases.
Highlights
The brain is composed of a complex circuitry of neurons that either send or receive different information acquired from the surrounding environment
The transport of mRNA to different subcellular domains, like axon growth cone, can contribute to spatiotemporal specific translation of the mRNA [56]. These results showed that the treatment of Netrin-1 induced the anterograde movement of β-actin mRNA while the deletion of the 3 untranslated region (3 UTR) of β-actin mRNA abolished this effect [36]
Axon guidance cues and receptors induce different signaling pathways that regulate the dynamics of F-actins, and the motility of the axon growth cone
Summary
The brain is composed of a complex circuitry of neurons that either send or receive different information acquired from the surrounding environment. Apart from signaling pathways, latest research has shown that Netrin-1 regulates axon guidance by influencing the local translation of different mRNAs, such as β-actin, Dscam, and tctp [36,37,51,52,53,54,55]. The transport of mRNA to different subcellular domains, like axon growth cone, can contribute to spatiotemporal specific translation of the mRNA [56] These results showed that the treatment of Netrin-1 induced the anterograde movement of β-actin mRNA while the deletion of the 3 untranslated region (3 UTR) of β-actin mRNA abolished this effect [36]. Netrin-1 can partake in the axon guidance of retinal ganglion cells by regulating the local translation of tctp mRNA
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