Our overall research interest is to understand how animals
recognize their ever-changing environment and how these
signals are translated into the appropriate changes in their
behavior and development. Environmental signals are recognized
by sensory neurons. For instance, thermosensory neurons
allow us to sense ambient temperature, while olfactory and
gustatory neurons are responsible for our complex senses
of smell and taste. We are particularly interested in investigating
the molecular mechanisms underlying the development and
function of olfactory and thermosensory neurons.
We study this problem in the sensory nervous system of
the model genetic organism C. elegans. C. elegans
exhibits a number of different sensory behaviors, including
responses to both volatile and aqueous compounds as well
as to temperature. All of these responses are easily assayed
in the lab. Moreover, the sensory neurons and the underlying
neuronal circuits required for these behaviors have been
identified. Taken together with the availability of powerful
genetic and genomic tools, C. elegans is a very attractive
system in which to explore the question of sensory neuron
development and function.
Current research projects are aimed at exploring three
broad questions.
1. How is complexity of function generated in the
sensory system? We are investigating the molecular
mechanisms that define the sensory properties of individual
sensory neuron types in C. elegans. How do different
types of olfactory neurons acquire their very specialized
functions? Using neuron-specific markers, we have carried
out genetic screens and identified genes required for the
correct generation and function of individual chemo- and
thermosensory neuron types. We have identified members of
well-conserved transcription factor families such as LIM-homeodomain
proteins and paired-type homeodomain proteins in these screens.
We have also analyzed the regulatory relationships among
identified genes, and placed them in genetic pathways.
These experiments have allowed us to suggest a few principles
for the generation of functional diversity in the sensory
system of C. elegans. First, distinct sensory neuron
subtype identities appear to be specified by members of
different transcription factor families. Second, we have
shown that a given factor can act at different steps in
the developmental hierarchies. Third, the role of each factor
appears to be constrained by the cellular context of expression.
Fourth, combinatorial transcription factor codes appear
to specify neuronal identities and finally, general sensory
neuron characteristics appear to be specified in parallel
to subtype-specific properties.
These results have provided a framework for us to study
how functional complexity is generated in the sensory system.
Interestingly, homologs of identified factors have also
been shown to play roles in the development and differentiation
of both sensory and non-sensory neuron types in other organisms
including vertebrates. We are now exploiting genetic and
genomic technologies to identify and characterize the complete
cascades of events required for the correct development
and function of each sensory neuron type.
A new interest in the lab is investigating how the morphological
characteristics of individual sensory neuron types become
specialized. In vertebrates, different neuron types exhibit
different dendritic morphologies and these structures are
critical for the correct functions of these neurons. Similarly,
in C. elegans, different sensory neurons exhibit
unique sensory morphologies. Moreover, similar to dendrites,
neuronal activity has been shown to play a role in maintaining
sensory morphologies in C. elegans. We are now exploring
how these unique structures arise during development and
how they are maintained through activity.
See research summaries of Saikat
Mukhopadhyay, Huatai
Xu, Eva
Nokes/Caron Gauthier, Melanie
Hong.
2. How is behavioral plasticity generated?
C. elegans can actively alter its sensory behaviors
in response to specific environmental conditions such as
overcrowding or starvation, and in specific life stages.
We have shown that this modulation occurs in part, via the
regulation of expression of olfactory receptor genes. Thus,
in addition to developmentally hard-wired mechanisms, olfactory
receptor genes are also regulated dynamically by environmental
signals. This is a unique and simple mechanism by which
an animal can rapidly alter its sensory behaviors. In genetic
screens, we have identified molecules that may play a role
in the regulation of olfactory receptor gene expression
by environmental cues. We are interested in further exploring
this very interesting mode of regulation, as well as characterizing
the nature of the input signals and the resulting behavioral
changes.
See research summaries of Kyuhyung
Kim/Mayumi Shibuya, Alexander
van der Linden.
3. What are the neural and molecular correlates of
thermosensory learning and memory? In spatial and
temporal thermal gradients, C. elegans exhibits a preference
for temperatures associated with food. Interestingly, this
thermal preference can be shifted upon shifts to different
temperatures. In collaboration with Dr. Aravi Samuel (Harvard),
we are using newly developed biophysical assays to dissect
the neural circuits and molecules underlying the sensation
of temperature and the memory of the cultivation temperature.Using
RNA isolated from isolated populations of a thermosensory
neuron type in microarray analyses, we have also identified
several new genes which play important roles in thermosensory
learning and memory. Our goal is to understand the neuronal
circuits underlying this fascinating behavior, and to identify
the molecules required for sensing and remembering temperature.
See research summaries of David
Biron, Sara
Wasserman.
Selected Recent Publications
Colosimo, M.E., Tran, S. and Sengupta, P. (2003) The divergent
orphan nuclear receptor ODR-7 regulates olfactory neuron
gene expression via multiple mechanisms in C. elegans.
Genetics, 165:1779-91.
Lanjuin, A., VanHoven, M.K., Bargmann, C.I., Thompson,
J.K. and Sengupta, P. (2003) Otx/otd homeobox genes
specify distinct neuron identities in C. elegans.
Dev. Cell, 5:621-33.
Satterlee, J.S., Ryu, W.S. and Sengupta, P. (2004) The
CMK-1 Ca2+/calmodulin-dependent
protein kinase I and the TAX-4 cyclic nucleotide-gated channel
regulate thermosensory neuron gene expression and function
in C. elegans. Curr. Biol. 14:62-8.
Melkman, T. and Sengupta, P. (2004) The worm's sense of
smell: Development of functional diversity in the chemosensory
system of C. elegans. Dev. Biol. 265:302-19.
Lanjuin, A. and Sengupta, P. (2004) Specification of chemosensory
neuron subtype identities in C. elegans. Curr. Op. Neurobiol.
14:22-30.
Colosimo, M.E., Brown, A., Mukhopadhyay, S., Gabel, C.,
Lanjuin, A., Samuel, A.D.T. and Sengupta, P. (2004) Identification
of thermosensory and olfactory neuron-specific genes via
expression profiling of single neuron types. Curr. Biol.14:2245-51.
Melkman, T. and Sengupta, P. (2005) Regulation of chemosensory
and GABAergic motor neuron development by the C. elegans
Aristaless/Arx homolog alr-1. Development
132:1935-1949.
Kim, Kyuhyung, Colosimo, M.E., Yeung, H. and Sengupta,
P. (2005). The UNC-3 Olf/EBF protein represses alternate
neuronal programs to specify chemosensory neuron identity.
Dev. Biol. 2005 Oct 1;286(1):136-48. .
Lanjuin A, Claggett J, Shibuya M, Hunter CP, Sengupta P.
(2006) Regulation of neuronal lineage decisions by the HES-related
bHLH protein REF-1. Dev Biol. 2006 Feb 1;290(1):139-51.
Epub 2005 Dec 22
Inada H, Ito H, Satterlee J, Sengupta P, Matsumoto K, Mori
I. (2006) Identification of guanylyl cyclases that function
in thermosensory neurons of Caenorhabditis elegans.
Genetics. 2006 Apr;172(4):2239-52.
Clark DA, Biron D, Sengupta P, Samuel AD. (2006) The AFD
sensory neurons encode multiple functions underlying thermotactic
behavior in Caenorhabditis elegans. J Neurosci. 2006
Jul 12;26(28):7444-51.
Biron D, Shibuya M, Gabel C, Wasserman SM, Clark DA, Brown
A, Sengupta P, Samuel AD. (2006) A diacylglycerol kinase
modulates long-term thermotactic behavioral plasticity in
C. elegans. Nat Neurosci. 2006 Dec;9(12):1499-505. Epub
2006 Nov 5.
Sengupta P. (2007) Generation and modulation of chemosensory
behaviors in C. elegans. Pflugers Arch. 2007
Jan 6; [Epub ahead of print]
van der Linden AM, Nolan KM, Sengupta P. (2007) KIN-29
SIK regulates chemoreceptor gene expression via an MEF2
transcription factor and a class II HDAC. EMBO J.
2007 Jan 24;26(2):358-70. Epub 2006 Dec 14.
View Complete Publication List on PubMed:
Piali Sengupta
Last update: January 26, 2007. E-mail comments
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