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| General introduction |
| We are interested in
developmental aspect of neural circuit
generation as well as later aspects of
maintenance and modification of neural
ciruits. Due to the complexity of the
vertebrate brain, we use the much simpler
nervous system of the nematode C.
elegans as a model system. Its genome
sequence, compact nervous system and
amenability to classical genetic screening
methods allows the identification of
molecules that are required for the neural
differentiation, the generation of specific
neural circuits and their maintenance.
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| Neuronal cell fate |
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We have focused our cell fate studies on
two synaptically connected neuron types
which process specific types of sensory
information, namely the ASE chemosensory
neurons, involved in taste responses and
its downstream synaptic partner, the AIY
interneuron class which processes
chemosensory information and integrates it
with various other sensory modalities
(Tsalik and Hobert, 2003, and references therein).
AIY Interneurons:
Over the past few years, we have identified
a set of transcriptional regulators that
are required for the appropriate
differentiation of the AIY interneurons
(Hobert et al., 1997, Altun-Gultekin et al., 2001). We have shown that these transcriptional regulators, both homeodomain proteins (ttx-3 and ceh-10), regulate the expression of an AIY cell-type specific gene battery (Wenick and Hobert, 2004). We are currently analyzing the function of several of these AIY-expressed genes. Since it is the co-expression of ttx-3 and ceh-10 specifically in AIY that drives AIY differentiation we are trying to understand how the expression of these two factors is regulated in AIY.
FIGURE 1 - AIY-interneuron specific gene battery. From Wenick
and Hobert, 2004
ASE sensory neurons:
The two bilaterally symmetric ASEL and ASER
neurons present a simple paradigm for a
fundamental problem in the neurosciences:
How is functional asymmetry ("laterality")
layered upon an anatomically symmetric
structure ? In the context of the ASE
neurons, which are morphologically
bilaterally symmetric, laterality is
displayed on the level of chemosensory
capacities, which are asymmetrially
distributed in ASEL and ASER. This
functional asymmetry correlates with the
asymmetric expression of a class of
putative chemoreceptor genes.
FIGURE 2 - gcy genes
We have used genetic mutant analysis to
reveal a cascade of gene regulatory
factors, including transcription factors
and miRNAs, that are required to establish
the functional asymmetries in the ASE
neurons (Chang et al., 2003; Johnston
and Hobert, 2004; Chang et al., 2004). We are continuing our genetic approaches to understand how the asymmetry of the ASE neurons is set up during development. (Johnston et al., 2006; Poole and Hobert, 2006; Sarin et al., 2007; Etchberger et al., 2007; ...)
FIGURE 3 - Regulatory cascade
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| Axon patterning |
We have undertaken a genetic analysis
of various aspects of axon patterning and
have identified genes involved in axon
collateral branching (Bülow
et al.,
2002), axon termination (Mehta
et al.,
2004), axon sprouting (Loria et al., 2003; Loria
et al. 2004) and axon midline
patterning (Bülow
et al., 2004a ; 2004b).
We
are focusing our efforts on a surprising
mechanism that we found to exist at the
ventral midline of C. elegans -
namely, a mechanism that is required to
maintain axon positioning after development
(Aurelio et al., 2002; Bülow
et al., 2004b; reviewed in Hobert and Bülow, 2003; Benard et al., 2006). We are trying to
understand how and why molecules are
specifically required to maintain the
structural intactness of axon fascicles.
The expression of one type of these
molecules, the ZIG proteins, is shown
below.
FIGURE 4 - Axon maintenance at the
ventral midline in C. elegans. The
PVT neuron, schematically shown in panel A
and B, expresses a set of zig genes
(panel C), which are required to maintain
axon position. For a review, see Hobert
and Bülow, 2003.
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Last update : 9/22/2008 by Baris
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