Assistant Professor
Ph.D., 1988
Washington University School of Medicine

RESEARCH

Molecular genetic analysis of neural development and behavioral modification

Animals undergo stereotypical behavioral modifications at different stages of development. The feeding behavior of Drosophila larvae is both physiologically and developmentally regulated. It offers an excellent paradigm for understanding how complex behaviors are centrally regulated, and how the timing of behavioral modification is coordinated with animal development. The knowledge from these studies is expected to provide valuable insights into understanding the biological basis of many human eating disorders.

We have identified a functionally conserved neuronal circuit comprising neurons expressing neuropeptide F (NPF) and its receptor NPFR1 in the Drosophila central nervous system. By using a combination of molecular genetic, neuroanatomic and behavioral approaches, we show that the NPF/NPFR1 system is persistently required to maintain the full attention to food acquisition by larvae. Moreover, NPF signaling is developmentally switched off in the larval central nervous system (CNS) at the end of the feeding phase, and overexpression of NPF prolongs feeding and prevents larval transition from feeding to food aversion. These findings provide functional evidence that the NPF/NPY signaling system is evolutionarily conserved. We are currently investigating the underlying molecular and neural mechanisms.

Molecular genetic analysis of alcohol related behaviors in the Drosophila model

The fly NPY-like system has another conserved role in acute alcohol response. We show that the NPF neuronal circuit is essential for mediating alcohol sensitivity, and flies ablated selectively of NPF or NPFR1 neurons are more resistant to alcohol sedation, while those overexpressing NPF are hypersensitive. We are now trying to understand how alcohol elicits sensitive response from the NPF neuronal circuit, and what are the molecular and cellular events that form a signaling cascade responsible for the sedative effect of alcohol. The Drosophila NPF system may be a useful model for understanding how alcohol affects the functioning of the CNS in humans.

The neural plasticity of the NPF neuronal circuit

The NPF neuronal circuit is responsive to and modified by diverse external cues including sugar and alcohol. These observations suggest that the NPF system may be a central neural interface that is capable of integrating a multitude of sensory inputs, and then modulating the motor outputs (reflected as behaviors) accordingly. We are currently investigating the molecular and cellular mechanisms for modulating NPF synthesis and release.

CONTACT INFORMATION

office (706) 542-1220, lab (706) 583-0593, fax (706) 542-4271, pshen@cellmate.cb.uga.edu

SEE ALSO

Biomedical & Health Sciences Institute

SUPPORT STAFF

	Xu

NAME		POSITION		E-MAIL
Jiang Chen		Post Doc		johnchen@uga.edu
Mo Li		Post Doc		moli@uga.edu
Kajari Mondal		Post Doc		kajari@uga.edu
Jie Xu		Grad Student		xujie@uga.edu
Yan Zang		Research Technician III		zy62@uga.edu

REPRESENTATIVE PUBLICATIONS

Wu, Q., Zhang, Y., Xu, J. & Shen, P. Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A 102, 13289-94 (2005).

Wu, Q., Zhao, Z. & Shen, P. Regulation of aversion to noxious food by Drosophila neuropeptide Y- and insulin-like systems. Nat Neurosci 8, 1350-5 (2005).

Wen, T., Parrish, C. A., Xu, D., Wu, Q. & Shen, P. Drosophila neuropeptide F and its receptor, NPFR1, define a signaling pathway that acutely modulates alcohol sensitivity. Proc Natl Acad Sci U S A 102, 2141-6 (2005).

Wu, Q., Wen, T., Lee, G., Park, J. H., Cai, H. and Shen, P. Developmental control of foraging and social behavior by the Drosophila neuropeptide Y-like system. Neuron 39, 147-61 (2003).

Belozerov, V.E., Majumder, P., Shen, P., and Cai, H.N. (2003) A Novel boundary element may facilitate independent gene regulation in the Antennapedia complex of Drosophila. EMBO J. 22, 3113-21 (2003).

Garczinski, S.F. Brown, M. R. Shen, Ping, and Murray T. F., and Crim, J.W (2002) Characterization of a functional neuropeptide F receptor from Drosophila melanogaster. Peptides. 23:773-80.

Shen, Ping and Cai, H.N.(2001) Drosophila neuropeptide F mediates integration of chemosensory stimulation and conditioning of the nervous system by food. J. Neurobiol 47:16-25.

Cai, H. N. and Shen, Ping (2001) The effect of cis-arrangement of chromatin insulators on their enhancer blocking activity Science 291:493-5.

Cai, H. N., Zhang, Z., Adams, J. R. and Shen, Ping (2001) Genomic context modulates insulator activity through promoter competition Development 128:4339-47

Brown, M.R., J.W. Crim, R.C. Arata, H.N. Cai, P. Shen. 1999. Identification of a Drosophila brain-gut peptide related to the NPY family. Peptides 20: 1035-1042.