Overexpression of Crmp2 induces the formation of multiple axons. Given that Rac1 can activate PI3K, this activation might form a positive feedback loop, which could sustain activity.Īkt signalling to GSK3β decreases the level of phosphorylation of microtubule-associated proteins, and thereby stabilizes microtubules. The PAR protein complex accumulates at the tips of axons, and mediates signalling from Cdc42 to Rac1, which influences the dynamics of actin filaments at the tip of the axon to enhance rapid axon outgrowth. These signalling pathways involve Akt and glycogen synthase kinase 3β (GSK3β), the mitogen-activated protein kinase (MAPK) cascade and small GTPases.
Signalling cascades downstream of phosphatidylinositol 3-kinase (PI3K) have been shown to have central roles in neuronal polarization. These extracellular signals might regulate the internal polarization programme. Each neurite has a dynamic motility during neuronal polarization, and the polarization mechanism involves positive and negative feedback.Įxtracellular signals, such as netrin and WNTs, regulate axonal orientation in Caenorhabditis elegans tissue. Evolutionarily conserved signalling cascades participate in the initial events of neuronal polarization.Īxonal outgrowth is the initial event of neuronal polarization in cultured hippocampal neurons. These two compartments acquire specific characteristics that enable neurons to transmit electrical signals. Neurons are highly polarized cells, and most develop a single axon and several dendrites.
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