Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 102

and were characterized by broad circumferential lamellipodia devoid of
filopodia. Live imaging of minor process formation in wild-type neurons
revealed that consistent with previous studies, these processes are initiated
by filopodial structures. In a few cases where Ena/VASP deleted neurons
formed processes, this also occurred through the thickening and subsequent
elongation of a single filopodium. Interestingly, the Ena/VASP deletion phe-
notype could be bypassed to different degrees by culturing the neurons on
laminin, meningeal fibroblasts, or through the expression of other proteins
previously shown to promote filopodia formation (e.g. myosin X and the
formin mDia2) or inhibition of myosin II (also see Kollins et al., 2009 ).
Thus, collectively, the data indicate that the neuronal cell body may have
multiple mechanisms that can be utilized to generate filopodia-dependent
minor processes in an environment-dependent manner.
A recent study has determined a role for F-BAR proteins in the regula-
tion of minor process formation ( Saengsawang et al., 2012 ). F-BAR proteins
have been involved in regulating the local degree of membrane curvature
during endocytosis and the formation of filopodia ( Suetsugu et al., 2010 ).
Genetic deletion of the F-BAR Cdc42-interacting protein 4 (CIP4) pro-
moted the rate of minor process development by cortical neurons. Con-
versely, overexpression of the protein impaired process formation and
resulted in prominent lamellipodial formation from neuronal cell bodies.
Unlike in nonneuronal cells, the effects of CIP4 on neuronal process forma-
tion are mediated through regulation of lamellipodia and not endocytosis or
filopodia, indicating a neuron-specific role for CIP4.
2.2. Extension and Guidance of Axons and Dendrites
Following the emergence of minor processes from the neuronal cell body,
the neuron differentiates one of these processes into an axon, and the rest
develop into dendrites. Axons and dendrites differ in significant ways. The
organization of microtubules is a prominent distinction between axons and
dendrites. Within axons, most microtubules have their fast growing + end
directed toward the distal tip of the axon. In contrast, in dendrites, the
orientation of microtubule + ends is almost equally distal and proximal.
Additionally, other cytological and molecular differences distinguish axons
and dendrites, but are not discussed here. For the purposes of this review,
it is relevant to keep in mind that axons and dendrites are different cellular
domains, and specific differences will be discussed on a per need basis.
During development, dendrites extend and branch in order to form a
dendritic field. Dendrites are usually in the order of a few 100 micrometers