interested in exploring the complex interactions between
an animal and its environment. Animals must recognize and
respond to multiple, complex environmental signals, and
translate this information into the appropriate behavioral
and developmental responses. What are the molecules, signaling
pathways and neuronal circuits that allow animals to respond
to environmental cues? Moreover, how does a memory of past
experience modify the animal's response?
molecular genetic approaches to study these issues in the
model organism Caenorhabditis elegans. C. elegans has a number of advantages for studying neuronal development
- C. elegans exhibits complex, experience-dependent
behaviors that can be readily quantified.
- Molecules required for different behaviors can
be easily identified using forward and reverse genetic
- All modern genomics and proteomics-based tools
can be applied in C. elegans, allowing us to identify
and analyze sets of molecules required for specific processes.
- The nervous system of C. elegans consists
of only 302 neurons, each of which can be easily identified.
- The connectivities of each neuron have been anatomically
mapped, allowing us to characterize the circuits underlying
- Individual neuron function can be monitored and
manipulated using both genetic and physiological tools.
- Finally, C. elegans is easy to work with
in practice - animals have a rapid lifecycle, can be asily
grown in the lab and strains can be frozen at -80° C.
- More information about C. elegans can be
found at WormBase.
projects in the lab are aimed at addressing three broad
How do sensory neurons acquire their unique functions?
other animals, C. elegans is attracted to, or avoids,
subsets of chemicals. Chemicals are recognized by a small
number of chemosensory neurons, each of which expresses
a defined subset of signaling genes such as chemoreceptors,
and exhibits a distinct cell type-specific morphology.
- Neuronal specification: We are investigating the molecular
mechanisms that confer cell type-specific properties onto
each of these sensory neuron types. We have identified transcription
factor cascades that are essential for the expression of
cell-specific signaling genes. We are also dissecting the
cis-regulatory mechanisms that drive gene expression in
defined cell types.
Examples of amphid ciliated sensory neurons: channel
and wing (ASH and AWB, respectively). (B) The forked
ciliary morphology of the AWB olfactory neuron type
visualized via cell-specific GFP expression (from Mukhopadhyay et al., 2008)
- Cilia development: Several chemosensory neuron types
exhibit highly specialized ciliary structures that are essential
for their unique sensory functions. We are exploring how
these specialized cilia develop and are maintained. In the
last few years, it has become evident that virtually every
cell type in a vertebrate is ciliated, and that ciliary
dysfunction contributes to a large number of disorders such
as Bardet-Biedl syndrome, polycystic kidney disease and
retinopathies. Cilia are formed via highly conserved mechanisms,
and C. elegans has proved to be an excellent model
organism for studying cilia development. However, little
is known about how specialized cilia are generated. We have
identified a transcription factor required for the formation
of one specialized cilia type, and have also shown that
sensory activity plays a role in the maintenance of cilia
structure. We are currently using a genetics and proteomics-based
approach to identify additional molecules and mechanisms
required for the generation and maintenance of these diverse
cilia structures. Given the high degree of conservation
in ciliary developmental mechanisms across phyla, we fully
expect that our work will be directly relevant in higher
How do animals sense their environment, and how do they
modulate their responses based on past experience?
interested in identifying the signaling pathways by which
animals respond to environmental chemicals. For instance, C. elegans monitors the presence of other nematodes
in its environment by monitoring the concentration of dauer
pheromone, a complex mixture of fatty acids that is produced
by these animals at all developmental stages. High concentrations
of dauer pheromone signal overcrowding and competition for
resources, and triggers a number of developmental and behavioral
- Pheromone signaling pathways: We have recently identified
receptors for dauer pheromone, and have shown that complex,
intracellular signaling pathways are required for pheromone-regulated
developmental and behavioral responses. We are further characterizing
these signaling pathways, and exploring how these pathways
are used to communicate within and among nematode species.
This information may be useful to combat infection by parasitic
- Environmental regulation of chemoreceptor genes: We
have shown that a simple mechanism by which past experience
can modulate C. elegans behavior is via dynamic regulation
of expression of chemoreceptor genes. We have identified
signaling cascades that regulate chemoreceptor gene expression,
and are investigating how information about the environment
and internal metabolic state is integrated to modulate chemoreceptor
gene expression and behaviors such as feeding.
||An osm-9p::gfp fusion gene is expressed in three
neuron types in control adult animals, but only in two
neuron types in adult animals that passed through the
alternate dauer developmental stage. (S.E.
- A cellular memory of developmental history: We have
recently found that C. elegans retains a memory of
its developmental history. Thus, animals exposed to specific
environmental conditions as larvae exhibit distinct gene
expression patterns and behaviors as adults. Preliminary
experiments suggest that this memory is maintained via epigenetic
mechanisms such as altered chromatin modification patterns.
These results are intriguing, since work in mammals has
implicated similar epigenetic regulatory mechanisms in governing
adult behaviors based on prenatal or early postnatal experience.
We are currently identifying the molecular mechanisms required
for the formation of this cellular memory.
How do animals respond to temperature?
much is known about how animals respond to sensory stimuli
such as light and chemicals, the neuronal and molecular
mechanisms underlying thermosensation is poorly understood. C. elegans exhibits a remarkably complex response
to temperature, such that the behavior of C. elegans on a thermal gradient is dictated by a memory of its
cultivation temperature. This experimental paradigm provides
an excellent opportunity to understand how a behavior is
generated from the level of single genes to the output of
a neuronal circuit(s).
that experience temperatures greater than their cultivation
temperature move down a thermal gradient towards their
cultivation temperature (cryophilic behavior). (D.
- Molecules required for thermosensory signal transduction: We are using genetic and genomic approaches to identify
putative thermoreceptors and signaling molecules required
for transduction of thermal information.
- Neuronal circuits required for thermosensation: We are
identifying the components of the thermosensory circuit.
Using genetically encoded calcium sensors, we are also monitoring
neuronal activity in response to thermosensory cues.
- Role of past experience in modulating thermosensory behaviors: We are investigating how past thermal and feeding experience
modulates thermosensory behaviors.
Selected Recent Publications (2008—present)
Omori Y., Zhao C., Saras A., Mukhopadhyay S., Kim W., Furukawa T., Sengupta P., Veraksa A., Malicki J. Elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8. Nat Cell Biol. 2008 Apr;10(4):437-44. [abstract]
Mukhopadhyay, S., Liu, Y, Qin, H., Lanjuin. A., Shaham, S. and Sengupta, P. (2008). Sensory signaling-dependent remodeling of olfactory cilia architecture in C. elegans. Dev. Cell. 14: 762-74 [PubMed].
Biron, D.*, Wasserman, S.*, Thomas, J.H.T, Samuel, A.D.T. and Sengupta, P. (2008) An olfactory neuron responds stochastically to temperature and modulates C. elegans thermotactic behaviors. PNAS 105:11002-11007 [abstract].
van der Linden, A.M., Wiener, S., You, Y-J., Kim, K., Avery, L. and Sengupta, P. (2008) The EGL-4 PKG acts with the KIN-29 SIK and KIN-2 PKA to regulate chemoreceptor gene expression and sensory behaviors in C. elegans. Genetics, 180:1475-1491 [abstract].
Kim, K., Sato, K., Shibuya, M., Zeiger, D.M., Butcher, R.A., Ragains, J.R., Clardy, J., Touhara, K. and Sengupta, P. (2009) Two chemoreceptors mediate the developmental effects of dauer pheromone in C. elegans. Science, 326:994-998 [abstract].
Nokes. E.B., van der Linden, A.M., Winslow, C., Mukhopadhyay, S., Ma, K. and Sengupta, P. (2009) Cis-regulatory mechanisms of gene expression in an olfactory neuron type in C. elegans. Dev. Dyn. 238:3080-3092 [abstract].
Sengupta, P. and Samuel, A.D. (2009) C. elegans: a model system for systems neuroscience. Curr. Opin. Neurobiol. 2009 Dec;19(6):637-43.[abstract]
Hall, S.E., Beverly, M.B., Russ, C., Nusbaum, C. and Sengupta, P. (2010) A cellular memory of developmental history generates phenotypic diversity in C. elegans. Curr. Biol. 2010 Jan 26;20(2):149-5. [abstract]
Kim, K., Kim, R. and Sengupta, P. (2010) The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans. Development, 2010 Mar;137(6):963-74. [abstract]
van der Linden A.M., Beverly M., Kadener S., Rodriguez J., Wasserman S., Rosbash M., Sengupta P. (2010) Genome-wide analysis of light- and temperature-entrained circadian transcripts in Caenorhabditis elegans. PLoS Biol. 2010 Oct 12;8(10):e1000503. [abstract]
Garrity P.A., Goodman M.B., Samuel A.D., Sengupta P. (2010) Running hot and cold: behavioral strategies, neural circuits, and the molecular machinery for thermotaxis in C. elegans and Drosophila. Genes Dev. 2010 Nov 1;24(21):2365-82. [abstract]
Sengupta P., Schedl T. (2011) Cellular reprogramming: chromatin puts on the brake. Curr Biol. 2011 Feb 22;21(4):R157-9. [abstract]
Wasserman S.M., Beverly M., Bell H.W., Sengupta P. (2011) Regulation of response properties and operating range of the AFD thermosensory neurons by cGMP signaling. Curr Biol. 2011 Mar 8;21(5):353-62. [abstract]
* - co-corresponding authors
View Complete Publication List on PubMed: Piali Sengupta
update: August 8, 2011.