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–  Molecular biology of pheromone detection in the mouse
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CATHERINE DULAC
Higgins Professor of Molecular and Cellular Biology
Howard Hughes Medical Institute Investigator

Email: dulac@fas.harvard.edu
Phone: 617-495-7893
Mail: The Biological Labs, 16 Divinity Avenue, Room 4017, Cambridge MA, 02138

Members of the Dulac Lab
List of Publications from PubMed

Research:

Our group is using molecular, genetic and electrophysiological techniques to explore the molecular and neuronal basis of innate social behaviors in the mouse. Two major lines of research are currently being pursued in the laboratory:

We are pursuing several projects at the molecular, cellular and systems levels in order to investigate the architecture and functional logic of neuronal circuits underlying pheromone signaling. The key questions we are addressing are: What is the nature of the mammalian pheromones and of the receptors that detect them? How are pheromone signals processed in the brain in order to generate species- and sex-specific behaviors such as aggression, mating, parental behavior, defensive behavior? What are the basic developmental processes that ensure appropriate neuronal connections between the olfactory sensory neurons and the brain? What are the respective roles of sensory experience and genetic information in setting appropriate pheromone-induced behaviors, and how are circuits underlying sex-specific behaviors established in the male and female brains?

The second set of projects explores the phenomenon of genomic imprinting in the brain, and the role of this mode of epigenetic modification in brain development and adult brain function. Genomic imprinting results in preferential expression of the paternally, or the maternally inherited allele of certain genes. We have recently used a genome-wide approach to characterize the repertoire of imprinted genes in the mouse embryonic and adult CNS. Our study uncovered over 1000 new loci with imprinted features, suggesting that imprinting is a major mode of epigenetic regulation in the brain. Imprinting appears to preferentially affect neural systems associated with social, motivational and homeostatic brain functions. Comparison of the imprinted gene repertoire in the adult hypothalamus and cortex, and in the developing brain demonstrates a complex spatiotemporal, species-, sex- and isoform-specific regulation. Genomic imprinting thus emerges as a major and dynamic mode of epigenetic regulation of brain function, with direct implications for the understanding of evolution and diseases. Future projects in the lab will aim at better understanding this mode of epigenetic regulation in mechanistic and functional terms.

 

Selected Publications:

Gregg, C., Zhang, J., Weissbourd, B., Luo, S., Schroth, G.P., Haig, D. and Dulac, C. (2010) High Resolution Analysis of Parent-of-Origin Allelic Expression in the Mouse Brain. Science, 329: 643- 648

Gregg, C., Zhang, J., Butler, J.E., Haig, D. and Dulac, C. (2010) Sex-Specific Parent-of-Origin Allelic expression in the Mouse Brain. Science, 329: 682- 685

Dulac, C. (2010) Brain function and chromatin plasticity. Nature 465:728-735

Ben-Shaul, Y., Katz, L.C., Mooney R.M., & Dulac, C. (2010) In-vivo Vomeronasal Stimulation reveals Sensory Encoding of Conspecific and Allospecific Cues by the Mouse Accessory Olfactory Bulb. PNAS 107:5172-5177.

Choi, P., Zakhary, L., Choi, W., Alvarez-Saavedra, E., Miska, E., Zhang, J., McManus, M., Harfe, B., Giraldez, A., Horvitz, R.H., Schier, A. and Dulac, C. (2008) Members of the miRNA-200 Family Mediate Olfactory Neurogenesis. Neuron 57:41–55.

Kimchi, T., Xu, J. and Dulac, C. (2007) A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448:1009-1014.

Wagner S, Gresser AL, Torello AT, Dulac C. (2006) A Multireceptor Genetic Approach Uncovers an Ordered Integration of VNO Sensory Inputs in the Accessory Olfactory Bulb. Neuron 50: 697-709.

Yoon H, L. W. Enquist and Dulac C. (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123, 669-682.

Tietjen, I., Rihel, J., and Dulac C. (2005) Single-cell transcriptional profiles and spatial patterning of the mammalian olfactory epithelium. Int. J. Dev. Biol. 49: 201-207

Loconto, J., Papes, F., Chang, E., Stowers, L., Jones, E., Takada, T., Kumanovics, A., Fisher-Lindahl, K., and Dulac, C., (2003). Functional Expression of Murine V2R Pheromone Receptors Involves Selective Association with the M10 and M1 Families of MHC Class Ib Molecules. Cell, 112: 607-618.

Tietjen, I., Rihel, J., Cao, Y., Zachary, L. and Dulac C., (2003). Single-cell transcriptional analysis of neuronal progenitors. Neuron, 38: 161-175.

Stowers, L., Holy, T., Meister, M., Dulac, C*. and Koentges, G. (2002) Loss of sex discrimination and male-male aggression in mice deficient in TRP2. Science , 295, 1493-1500.* corresponding author.

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