Neuronal polarization: From spatiotemporal signaling to cytoskeletal dynamics

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Neuronal polarization establishes distinct molecular structures to generate a single axon and multiple dendrites. Studies over the past years indicate that this efficient separation is brought about by a network of feedback loops. Axonal growth seems to play a major role in fueling those feedback loops and thereby stabilizing neuronal polarity. Indeed, various effectors involved in feedback loops are pivotal for axonal growth by ultimately acting on the actin and microtubule cytoskeleton. These effectors have key roles in interconnecting actin and microtubule dynamics – a mechanism crucial to commanding the growth of axons. We propose a model connecting signaling with cytoskeletal dynamics and neurite growth to better describe the underlying processes involved in neuronal polarization. We will discuss the current views on feedback loops and highlight the current limits of our understanding.HighlightsFeedback loops drive axon specification by promoting growth of one neurite and inhibiting growth of the other neuritesFeedback loops are fueled by the neurite-length dependent accumulation of proteins, including polarity effectorsMany polarity effectors are part of neurite-growth promoting signaling pathways and feedback loopsPolarity effectors increase neurite growth by regulating the growth-cone cytoskeleton or membrane dynamicsDuring neurite growth, the actin- and microtubule cytoskeleton are tightly coordinated with membrane dynamics

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