Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans
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Abstract
Nociceptive neurons innervate the skin with complex dendritic arbors that respond
to pain-evoking stimuli such as harsh mechanical force or extreme temperatures. Here
we describe the structure and development of a model nociceptor, the PVD neuron of
C. elegans, and identify transcription factors that control morphogenesis of the PVD
dendritic arbor. The two PVD neuron cell bodies occupy positions on either the right
(PVDR) or left (PVDL) sides of the animal in posterior-lateral locations. Imaging
with a GFP reporter revealed a single axon projecting from the PVD soma to the ventral
cord and an elaborate, highly branched arbor of dendritic processes that envelop the
animal with a web-like array directly beneath the skin. Dendritic branches emerge
in a step-wise fashion during larval development and may use an existing network of
peripheral nerve cords as guideposts for key branching decisions. Time-lapse imaging
revealed that branching is highly dynamic with active extension and withdrawal and
that PVD branch overlap is prevented by a contact-dependent self-avoidance, a mechanism
that is also employed by sensory neurons in other organisms. With the goal of identifying
genes that regulate dendritic morphogenesis, we used the mRNA-tagging method to produce
a gene expression profile of PVD during late larval development. This microarray experiment
identified>2,000 genes that are 1.5X elevated relative to all larval cells. The enriched
transcripts encode a wide range of proteins with potential roles in PVD function (e.g.,
DEG/ENaC and Trp channels) or development (e.g., UNC-5 and LIN-17/frizzled receptors).
We used RNAi and genetic tests to screen 86 transcription factors from this list and
identified eleven genes that specify PVD dendritic structure. These transcription
factors appear to control discrete steps in PVD morphogenesis and may either promote
or limit PVD branching at specific developmental stages. For example, time-lapse imaging
revealed that MEC-3 (LIM homeodomain) is required for branch initiation in early larval
development whereas EGL-44 (TEAD domain) prevents ectopic PVD branching in the adult.
A comparison of PVD-enriched transcripts to a microarray profile of mammalian nociceptors
revealed homologous genes with potentially shared nociceptive functions. We conclude
that PVD neurons display striking structural, functional and molecular similarities
to nociceptive neurons from more complex organisms and can thus provide a useful model
system in which to identify evolutionarily conserved determinants of nociceptor fate.
Copyright 2010 Elsevier Inc. All rights reserved.