How does an axon grow?

Abstract

How do axons grow during development, and why do they fail to regrow when injured? In the complicated mesh of our nervous system, the axon is the information superhighway, carrying all of the data we use to sense our environment and carry out behaviors. To wire up our nervous system properly, neurons must elongate their axons during development to reach their targets. This is no simple task, however. The complex morphology of axons and dendrites puts neurons among the most intricate and beautiful cells in the body. Knowledge of how neurons extend axons and dendrites, elongate at a particular rate, and stop growing at the proper time is critical to understanding the development of our nervous system, yet the regulation of these processes is poorly understood. Considerable attention in recent years has focused on understanding how growth cones are guided and steered through complicated pathways (for review, see Schmidt and Hall 1998;Mueller 1999), and even how neurons initiate new processes (for review, see Da Silva and Dotti 2002), but what mechanisms are involved in elongation itself? Are environmental signals needed to drive axon growth and, if so, what are the intracellular molecular mechanisms by which they induce elongation? What controls the rate of axon growth? How do CNS neurons know whether to extend axons or dendrites? Is the signaling of axon versus dendrite growth attributable to different extracellular signals, different neuronal states, or both? All of these questions bear critically on our understanding of axon growth and here I review recent answers and approaches to the above questions, and highlight their relevance during development, injury, and disease.

Postnatal growth of the human optic nerve

“…Interestingly, it is still unknown whether postnatal ON axonal growth occurs as a diffuse phenomenon, or whether there is a specific focal site (for example, at the junction of the eye and ON). 5 Because the majority of ON growth occurs by 3 years of age, this postnatal interval likely represents a period of increased sensitivity and potential damage. Conversely, the factors associated with postnatal growth of the human ON may also increase early resistance and recovery to ON stressors such as elevated IOP, compared with treatment in adulthood.…”

Molecular Mechanisms, Biological Actions, and Neuropharmacology of the Growth-Associated Protein GAP-43

“…Although ribosomes, HuD, and GAP-43 mRNA have been detected in axonal growth cones [86], this may be a secondary site of synthesis, as axonal protein synthesis does not appear to be necessary if protein synthesis in the cell body is available [105]. It is nevertheless possible that local protein synthesis is necessary to provide growth-related proteins that sensitize the growth cone to guidance cues [35]. It has been shown that inhibitors of protein synthesis prevent the turning of retinal growth cones in response to chemotropic agents such as netrin-1 [14].…”

“…The fact that this does not occur in the central nervous system has been attributed to an inhibitory glial environment as well as to a loss of both intrinsic and extrinsic factors [35]. In adult mammals, retinal ganglion cells cannot regenerate their axons after optic nerve injury, and they subsequently undergo apoptotic cell death [52].…”

“…It is now clear that they extend in response to extracellular agents [35]. These agents are typically neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5), as well as the extracellular matrix molecules laminin, heparan sulfate proteoglycans, and the cell adhesion molecules L1 and N-cadherin [35].…”

Propofol-induced changes in neurotrophic signaling in 14-day-old rat forebrain

“…Od tada je u brojnim studijama pokazano da BDNF ojačava ekscitatorne (glutamatne) sinapse i oslabljuje inhibitorne (GABAergičke) sinapse. Kang i Schuman (1995) (Goldberg, 2003). U ove stimuluse spadaju neurotrofini, vanćelijski matriksni molekuli laminin, heparan sulfat proteoglikani, kao i ćelijski adhezivni molekuli kao što su L1 i N-kadherin (Goldberg, 2003).…”