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In-Depth Information
B. Axon Guidance and Dendrite Morphogenesis
Following fate determination, neurons will grow two types of processes: den-
drites, which collect information from upstream cells, and axons, which pass infor-
mation to downstream targets. Axon guidance and dendrite morphogenesis involve
complex interactions between intrinsic pathways and extrinsic cues. In their pioneer-
ing work, Hedgecock et al. identified the first group of genes that are required for
axon growth and guidance using fluorescein dye-filling technique (
Hedgecock et al.,
1985
). With the use of fluorescent protein labeling which allows for clear visuali-
zation of axon paths, the roles of many genes essential to axon guidance including
the conserved UNC-6/Netrin and the SLT-1/slit signaling pathways have been deeply
investigated. One such example of axon guidance studies is from the study of
mechanosensory neuron AVM. The guidance of AVM axons is coordinated by both
attraction to a ventral netrin signal (via the UNC-40/DCC receptor) and repulsion
from a dorsal Slit signal (via the SAX-3/Robo receptor) (
Culotti, 1994; Hao et al.,
2001
).
It is generally perceived that most C. elegans neurons
'
dendrites have relatively
simple morphology, based on images of EM reconstruction and static antibody
staining. One great advantage of using transgenic XFP labeling of neurons is the
increasing realization that numerous C. elegans neurons exhibit complex morphol-
ogy and that the axon and dendritic arbors display dynamic features. For example,
cell-type labeling revealed that the PVD neuron elaborates complex dendrite tree. A
recent study has discovered that a cell fusion gene eff-1 is required for the dendritic
tree formation of PVD neurons (
Oren-Suissa et al., 2010
). Additionally, transgenic
double-labeling of neurons with their neighboring cells has also begun to reveal
intercellular mechanisms in the development of neurons. For example, through a
genetic screen using cell-type specific XFP labeling for amphid neurons and glial
cells, it was shown that formation of amphid dendrites utilizes a ''retrograde exten-
sion'' mode (
Heiman and Shaham, 2009
).
C. Synapse Formation and Specificity
Just like axon guidance can be clearly studied at single process resolution,
Single synapses can be studied in vivo by expressing synaptic fluorescent pro-
teins (
Nonet, 1999
). Using XFP labeling synapses in visual genetic screens,
multiple signaling pathways have been identified to regulate formation of pre-
synaptic terminals and postsynaptic structures (
Jin, 2005
). Further studies in
other organisms have shown that most of these synapse-formation molecules
are functionally conserved from C. elegans to mammals. For example, the con-
served giant PHR protein, RPM-1, was discovered by its effects on synapse
organization. Loss of function of rpm-1 reduces synapse number and alters
synapse morphology (
Schaefer et al., 2000; Zhen et al., 2000
). Further mecha-
nistic dissection revealed that RPM-1 acts as a ubiquitin E3 ligase to control
activation of the conserved DLK-1 MAP kinase signaling pathway (
Nakata et al.,
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