Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 111

filopodia, but the mechanism of filopodial formation can be tapped into in
a manner relatively independent of the specific cell type, at least by some
molecules.
A few studies have also suggested that the mechanisms underlying
aspects of filopodia initiation, or development, differ at the subcellular level.
For example, Meberg and Bamburg (2000) found that overexpression of
actin depolymerizing factor in embryonic cortical rat neurons increases and
decreases the number of filopodia at growth cones and along the axon shaft,
respectively. In our own studies, we have found that introduction of domi-
nant negative Rac1 into chicken sensory neurons decreases the number of
both axonal and growth cone filopodia ( Spillane et al., 2012 ). In contrast,
introduction of dominant negative Cdc42 only decreased the number of
growth cone filopodia without affecting the number of axonal filopodia
in the same neurons. Consistent with this observation, a study investigating
Cdc42 activity levels in axons and growth cones found high levels in the
peripheral domain of growth cones, but minimal levels in the axon shaft
( Myers et al., in press ). Furthermore, the levels of Cdc42 activity detected
in the axon were not affected by cell permeable peptide-mediated blockade
of Cdc42, while the levels at the growth cone dropped to levels analogous
to those detected in the axon. Similarly, the induction of filopodia by nerve
growth factor and PI3K activation at the growth cone and along the axon
shaft is independent and dependent on axonal protein synthesis, respectively
( Spillane et al., 2012 ; also see Section 3.4 ). Dendritic filopodia also exhibit
differences depending on whether they arise from the dendritic shaft or at
the growth cone ( Portera-Cailliau et al., 2003 ). Analysis of the developing
dendrites of cortical neurons in slice cultures revealed that the motility,
length and density of filopodia is greater at the growth cone than along
the dendrite shaft, and manipulating neuronal synaptic activity differently
affects shaft and growth cone filopodia. Thus, studies of neuronal axons,
dendrites and growth cones have begun to unveil subcellular differences in
aspects of the mechanisms underlying the regulation of filopodia.
An outstanding example of how filopodia can vary in structural orga-
nization was provided by a study comparing the ultrastructure of dendritic
filopodia to growth cone and axonal filopodia using platinum replica elec-
tron microscopy ( Korobova and Svitkina, 2010 ). In contrast to “conven-
tional” filopodia, which exhibit a tightly bundled parallel array of actin
filaments in their shaft, dendritic filopodia were found to contain a hybrid
of long linear filaments with Arp2/3 complex branched filaments along the
shaft. Furthermore, dendritic filopodia did not contain the actin bundling