![]() Thus dissociation of the cells causes total axon removal. When cortical neurons from newborn rat are dissociated, the axon is lost, but a region of the apical dendrite that has mixed microtubule polarity can remain attached to the cell body. In fact, the process of regenerating an axon from a dendrite does seem to be accompanied by changing the microtubule cytoskeleton from the dendritic polarity to the axonal one. Thus if a dendrite becomes or grows an axon one might expect that microtubule polarity would have to be rearranged. In dissociated hippocampal neurons, dendrite specification and growth occurs at the same time that minus-end-out microtubules enter dendrites ( Baas et al., 1989), and loss of the minus-end-out population of microtubules from dendrites results in overall loss of dendritic character ( Yu et al., 2000). The minus-end-out microtubules in dendrites have been linked to dendritic identity. In cultured mammalian neurons, axons have uniform polarity microtubules with plus ends distal to the cell body (plus-end-out), whereas dendrites have mixed polarity with about half plus-end-out and half minus-end-out microtubules ( Baas et al., 1988 Stepanova et al., 2003). Microtubules in axons and dendrites have different polarity, and several different approaches have suggested that this arrangement is crucial for overall neuronal polarity. It is not known how neuronal polarity is completely rearranged after axon removal to allow a dendrite to become or grow a new axon. Thus in several systems, neurons initiate regeneration after axon removal by converting a dendrite to a new axon, or at least growing a new axon from the tip of a dendrite. These new processes contain tau immunoreactivity, like axons, and are presynaptic ( Gomis-Ruth et al., 2008). As in earlier in vivo studies, close axotomy induced new growth from dendrites. Axons of mouse hippocampal neurons in dissociated and slice culture were severed at different distances from the cell body ( Gomis-Ruth et al., 2008). Axon removal experiments have also been performed in cultured neurons. Similar observations of growth of axon-like processes from dendrites in vivo have been made in cat motoneurons and interneurons after proximal axotomy ( Rose et al., 2001 MacDermid et al., 2002 Fenrich et al., 2007), as well as several types of rodent neurons ( Cho and So, 1992 Hoang et al., 2005). Subsequent analysis showed that at the ultrastructural level the new processes emerging from dendrites after axon removal had axonal features, for example, abundant neurofilaments ( Hall et al., 1989). This is in contrast to axon injuries further from the cell body that induce regrowth from the axon as well as increased dendritic growth. In sea lampreys, complete removal of axons from hindbrain neurons triggers new growth from dendrites that extends beyond the normal dendritic field ( Hall and Cohen, 1983). Studies performed in several systems suggest that neurons have a tremendous capacity for axon regeneration, even in response to total axon removal. Complete axon removal is the most severe type of axon injury a neuron can sustain, and it renders the cell nonfunctional as it can no longer send signals. Unlike many other cell types, most neurons are not replaced during an animal's lifetime, yet they can be damaged by physical traumas or immune attack. ![]() Axons and dendrites have distinct proteins targeted to them, as well as different cytoskeletal arrangements ( Craig and Banker, 1994). Neurons are highly polarized cells many neurons have several dendrites that receive information and a single axon to send information. We conclude that regulation of microtubule dynamics and polarity in response to JNK signaling is key to initiating regeneration of an axon from a dendrite. In addition, we find that JNK signaling is required for both the up-regulation of microtubule dynamics and microtubule polarity reversal initiated by axon injury. Only neurons with a single dendrite that reverses polarity are able to initiate tip growth, and normal microtubule plus-end dynamics are required to initiate this growth. ![]() After one dendrite reverses its microtubules, it initiates tip growth and takes on morphological and molecular characteristics of an axon. Two major microtubule rearrangements are specifically induced by axon and not dendrite removal: 1) 10-fold up-regulation of the number of growing microtubules and 2) microtubule polarity reversal. We show that Drosophila neurons in vivo can convert a dendrite to a regenerating axon and that this process involves rebuilding the entire neuronal microtubule cytoskeleton. For neurons to recover from complete axon removal they must respecify a dendrite as an axon: a complete reversal of polarity. Axon regeneration is crucial for recovery after trauma to the nervous system. ![]()
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