Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 103

in length at most, serve as the “antennae” of neurons, and establish synaptic
contacts with incoming axons. In contrast, axons have to extend relatively
long distances throughout the developing embryo and must be properly
targeted to the correct nervous system region in order to establish synap-
tic contacts with the dendrites of appropriate target neurons. The process
by which extracellular signals determine the direction of the extension of
axons is termed axon guidance/path finding . Axon elongation and guidance
is mediated by a specialized motile structure located at the tip of the axon
termed the growth cone (Fig. 3 . 1 A). Axonal growth cones are characterized
by two major domains, the peripheral (P) and central (C) domain. The
P-domain consists of lamellipodia and filopodia. The C-domain is the inter-
face between the end of the axon shaft proper and the P-domain (Fig. 3 . 1 A).
The C-domain contains few actin filaments, relative to the P-domain, but
is enriched in the + tips of microtubules. Just proximal to the C-domain,
protrusive activity is shut down giving rise to a mostly quiescent axon shaft
and the transition between the dynamic growth cone and the axon shaft
is termed the growth cone neck (Fig. 3 . 1 A). Extending dendrites also have
growth-cone-like structures at their tip, but have received much less atten-
tion than axonal growth cones. The growth cones of extending axons inter-
act with soluble signals, the surfaces of other cells and the extracellular
matrix and interpret these extracellular signals in order to determine the
direction of process extension. The guidance of neuronal processes is thus
driven by extracellular signals, which result in changes in signaling pathways
within the growth cone, ultimately leading to cytoskeletal reorganization
and redirection of the extending growth cone.
The extension of established axons proceeds through a series of growth
cone cytoskeletal and morphologic rearrangements, which can be broken
into three distinct phases ( Dent and Gertler, 2003 ). The first phase is termed
protrusion and involves the P-domain. During this phase, the growth cone
extends actin-filament-dependent lamellipodia and/or filopodia. The sec-
ond phase is termed engorgement and involves the C-domain. Engorgement
is a microtubule-based phase of extension and refers to the movement of
microtubule tips into recently protruded domains of the growth cone. The
forward advance of microtubule tips can occur through microtubule + end
polymerization or, to some degree, the transport of subsets of axonal micro-
tubules. Microtubules engage actin filaments in the P-domain, and the ret-
rograde flow of actin filaments from the P-domain toward the C-domain
serves to prevent microtubules from extending forward ( Schaefer et al.,
2002 , 2008 ). Inhibition of myosin II, which mediates retrograde flow, allows