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Actin filaments used to build filopodia are nucleated
de novo
from the pool
of cytoplasmic monomeric actin, a task accomplished by multiple fami-
lies of actin nucleation factors discussed in Section
4.2
. Additional pro-
teins regulate the rate of polymerization, stability and depolymerization of
filaments following nucleation, discussed in Section
4.3
. Importantly, the
mere availability of filaments is insufficient for proper cellular physiology.
Therefore, cells utilize a large number of proteins to generate specific struc-
tures using actin filaments, further discussed in Section
4.2
(
Michelot and
Drubin, 2011
).
Most, if not all, metazoan cells can form filopodia. Indeed, filopodia have
fundamental roles throughout the life cycle of metazoans. As a few exam-
ples, during early embryonic development, filopodia have roles in cell-cell
contacts and communication during blastulation and grastrulation (
Nakat-
suji, 1974
;
Satoh, 1978
). Similarly, filopodia serve to anchor cells from dif-
ferent germ layers in the primitive streak of both rat and chicken embryos
(
Solursh and Revel, 1978
). The filopodia of endothelial cells likely have
roles in sprouting angiogenesis (
De Smet et al., 2009
;
Eilken and Adamns,
2010
). In cancer, filopodia serve as invasive structures promoting metastasis
(Machesky, 2010). Atlhough filopodia are prominent features of many cell
types, this review focuses on primary neurons in vivo and in vitro. Neurons
exhibit the most complex and polarized morphology of any metazoan cell,
and the morphogenesis of neurons is completely dependent on the actin
and microtubule cytoskeleton. As detailed in Section
2
, due to the many
varied function of filopodia in neurons, the neuron is an excellent model
system for addressing a multitude of questions regarding the biology of
filopodia. Section
2
of this chapter emphasizes the varied roles of filopodia
in the biology of neurons, and it is intended as a primer for readers not
familiar with neuroscience. Sections
3-5
focus on the cellular mechanisms
underlying the regulation of neuronal filopodia, and the mechanisms that
link actin-filament-based filopodia to microtubules.
2. ROLES OF FILOPODIA IN THE DEVELOPMENT
OF NEURONAL MORPHOGENESIS AND CIRCUIT
FORMATION
2.1. Initiation of Axons and Dendrites
Following exit from the mitotic cycle in the developing neural tube, dif-
ferentiated central nervous system neurons become postmitotic and migrate
through the developing nervous system to find their appropriate location
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