Research Description:
Untitled Document
Nerve cells (neurons) provide a rapid communications network that is responsible
for producing behavior. The networks are functionally analogous to the electronic
circuits within a computer. Nervous systems, like computers, rely on their components
to b e precisely connected. Developing neurons send out cellular processes that
distinguish between appropriate and inappropriate targets and form precise connections
(a process termed target specificity). The goal of my laboratory's research is
to understand the genetic and molecular basis for this specificity. A small, free-living
nematode, Caenorhabditis elegans, is particularly well suited for studying this
question.
Research on C. elegans has provided an exceptionally detailed description
of the structure of the animals's nervous system. Both the synaptic connectivity
and the lineal origin of the 302 neurons in the adult are known. This description
serves as a foundation for studies investigating the genetic control of neuronal
development. A number of mutations exist that disrupt either the production
or the differentiation of the neurons. The methodology now exists for performing
sophisticated cellular, genetic an molecular analyses of these genes and their
products.
We are currently studying two sets of motorneurons involved in locomotion.
One set is born and differentiates before the animal hatches and ultimately
innervates dorsal muscle. The second set is born after the animal hatches and
innervates ventral muscle. In spite of these differences the two sets of motorneurons
share many features and appear to be produced by very similar genetic programs.
Currently, 20 genes are known that when mutated, cause identical changes in
both neuron classes. Only one gene is known that specifically affects one of
these two motorneuronal classes. Interestingly, mutations in this gene cause
the late-arising neurons to become identical to the early-arising set (i.e.,
they innervate dorsal instead of ventral muscle). Insight into how the product
of this gene diverts the target specificity of an entire class of motorneurons
will be gained by cloning and sequencing the gene. A complete genetic characterization
will allow the determination of when (at what developmental stage ) and where
(what cells) the gene is expressed as well as the identification of other genes
involved in the differentiation of these two sets of neurons. Light and electron
microscopy techniques are being used to compare the morphological development
of the motorneurons in the mutant with that of the wild-type animal.
In C. elegans, individual neurons arise from precise lineages and express
unique combinations of differentiated characteristics. We are attempting to
exploit this to understand the "genetic blueprint" responsible for
neural specificity.
Lateral view of the mid-body region of C. elegans showing GABA-like immunoreactivity
of the D motoneurons. Structurally, the D motoneurons are composed of processes
in the dorsal cord (upper), processes in the ventral cord (lower) and connecting
commissures shown running circumferentially.
Recent Publications:
Shan, G., Kim, K., Li, C., & Walthall, W (2005) Convergent Genetic Programs Regulate4 Similarities and Differences Between Related Motor Neuron Classes in Caenorhabditis elegans. Developmental Biology 280, 494-503.
Levine, MZ, Harrison, PJH, Walthall WW, Tai, PC & Derby CD (2001) A CUB-serine protease in the olfactory organ of the spiny lobster Panulirus argus J. Neurobio. 49, 277-302
H. Mimi Zhou and W. W. Walthall, (1998). UNC-55, an Orphan Receptor, Orchestrates Synaptic Specificity among Two Classes of Motor Neurons in Caenorhabditis elegans. The Journal of Neuroscience 18: 10438-10444.
Walthall, W.W. (1990). Metamorphic-like changes in the nervous system of the nematode Caenorhabditis elegans. J. Neurobio. 7:1085-1091.
Walthall, W.W. and Chalfie, M. (1988). Cell-cell interactions in the guidance of late-developing neurons in Caenorhabdits elegans. Science, 239:643-645.
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