Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 107

understanding the formation of collateral branches is a fundamental issue
in neuroscience.
In vivo and in vitro axon collateral branches are initiated as axonal filo-
podia ( Gallo, 2011 ). Axons generate many transient filopodia, a subset of
which matures into collateral branches. Similar to the main axon shaft, col-
lateral branches are supported by a microtubule array. The entry of axonal
microtubules into axonal filopodia is considered to be fundamental to be
ability of the filopodium to mature into a branch. The formation of axonal
filopodia is under control by target tissue derived signals. The regulation of
axonal filopodial formation and dynamics has been most intensively studied
in the context of the branching of retinal axons and cortical axons. For the
purpose of this review and didactics, I will focus on the development of
branches along cortical axons projecting into the spinal cord ( O'Leary et al.,
1990 ). During development, cortical neurons project axons into the spinal
cord. The axons initially grow past the developing pons. As the pons devel-
ops, the segments of axons adjacent to the pons begin to exhibit higher
rates of axonal filopodia formation ultimately culminating in the matura-
tion of a subset of these filopodia into collateral branches that extend into
the pons ( Bastmeyer and O'Leary, 1996 ). In vitro coculture studies using
explants of pons tissue have determined that the pons releases soluble fac-
tors, which promote the formation of axonal filopodia and branches ( Sato
et al., 1994 ). It is also noteworthy that the process of branching is not simply
controlled by factors that promote to formation of axonal filopodia and
branches, but also by factors that inhibit the formation of branches or pro-
mote their retraction ( Gibson and Ma, 2011 ; Gallo, 2011 ). Thus, a balance of
branch promoting and inhibitory factors ultimately sculpts the architecture
of axons.
Direct evidence for the dependence of branching on axonal filopodia
was presented in the previously discussed study by Dwivedy et al. (2007;
Section 2.2) . A major finding of this study was that although axons eventu-
ally found their path to their synaptic target regions, the optic tecum, when
they arrived, the axons exhibited a near-complete failure to generate axonal
filopodia and collateral branches. These exciting in vivo findings are con-
sistent with many in vitro studies addressing the role of axonal filopodia in
branching. This study also underscores the necessary role of axonal filopodia
in the process of branching.
Similar to axons, dendrites form branches from filopodial precursors
in vivo. Contact of a dendritic filopodium with an appropriate synaptic
partner axon initiates calcium-based mechanisms leading to the formation