Biology Reference
In-Depth Information
1. REGULATION OF AXON GROWTH AND
REGENERATION
The nervous system is comprised of 10
11
neurons, which are
programmed and plastic in at least two respects: the neurons are programmed
to attain precise neuronal morphology and become integrated into neural
circuit during development. Underlying neuronal morphogenesis and
wiring of the neural circuit are developmental programs that establish
neuronal polarity, promote axon growth, and initiate synaptic connections.
On the other hand, neurons are remarkably plastic to some extent, as even
after injury, damaged axons can regenerate, when provided with appropriate
conditions. These realizations have led to intense efforts in understanding the
molecular mechanisms that underlie axon growth and regeneration.
1.1. Axon growth under normal condition
During development, neurons undergo an initial polarization process when
one neurite acquires axon identity, and other neurites differentiate to
become dendrites. After specification of axon-dendrite polarity, axon
elongation which depends on the forward movement of the growth cone,
takes place. To support axon growth, the growth cone integrates and trans-
duces the extracellular signals to intracellular responses through orchestrated
cytoskeletal reorganization, transcription, and translation programs, as well
as transport and trafficking cascades (
Polleux & Snider, 2010
).
1.2. Injury-induced signals upon axon damage
After injury, axon regrowth is more complicated because the neuron must
survive, reseal its damaged membrane, and transform the proximal lesion site
into a growth cone-like motile structure that needs to extend through a
comparatively mature and complex environment. Upon axon transection,
the most immediate events include calcium influx and subsequent anti-
dromic action potential as the disrupted axon exposes its interior to the
external environment. In many axon regeneration models, such calcium en-
trance is necessary for reforming a growth cone and initiating regenerative
pathways (
Bradke, Fawcett, & Spira, 2012
). In addition to these priming
changes, multiple injury signals are generated by the cut axonal terminals,
and are retrogradely transported along the axon shafts to the cell bodies
to initiate transcription and translation programs for axon regeneration.
For
instance,
local
release of neuropoietic cytokines
such as ciliary
