Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 99

( Faux et al., 2012 ). Peripheral nervous system neurons develop from migrat-
ing neural crest cells, or from placodes that form in situ within a tissue.
Neural crest cells arise from the dorsal neural tube and migrate throughout
the embryo and give rise to both neurons and nonneuronal cells. Sensory
ganglia are the structures that allow the central nervous system to receive
sensory information and also mediate proprioception. Neural crest cells
converge and form cell aggregates which subsequently differentiate into a
variety of sensory neurons and ganglia. Migration of central nervous system
neuronal cell bodies and neural crest cells depends on the establishment
of polarized leading edges, which serve as the machinery for sensing and
responding to the extracellular environment ( Krispin et al., 2010 ; Manent
et al., 2011 ). Central nervous system neurons form dendrites and axons,
while some peripheral nervous system neurons (e.g. dorsal root ganglion
neurons) only form axons. In the case of central nervous system neurons,
the cell body initially extends multiple “minor processes,” which are undif-
ferentiated and cannot be parsed into axons or dendrites. However, fol-
lowing the extension of these minor processes, the neuron selects one for
differentiation as the axon, while the rest differentiate into dendrites. The
issue of the specification of the axon and dendrites from the multiple undif-
ferentiated minor processes formed by neurons undergoing morphogenesis
is not discussed here, and the reader is directed to previous reviews of the
topic ( Cheng and Poo, 2012 ).
The leading edge of neuronal processes starts as a lamellipodial protru-
sion from the neuronal cell body and exhibits filopodia, or in some cases,
filopodia form without lamellipodia. In vitro studies of the initial stages of
protrusion have unveiled fundamental aspects of the cytoskeletal machinery
of the early stages of axon and dendrite formation from cell body protru-
sions. The formed axon and dendrites are dependent on both actin filaments
and microtubules for their proper function. Similarly, both actin filaments
and microtubules contribute to the emergence of axons and dendrites. The
regulation of cytoskeletal dynamics in filopodia extending from neuronal
cell bodies has emerged as one of the earliest steps in the formation of axons
and dendrites and will be discussed further. Insights into the formation of
filopodia during preaxon/dendrite formation stages of development, and
the maturation of filopodia into neuronal processes, were obtained through
careful analysis of the process using a variety of imaging modalities ( Smith,
1994a,b ). Differential interference contrast imaging revealed that an early
step in the formation of neuronal processes is the invasion of the filopo-
dium by cytoplasm, which causes the filopodium to swell and increase in