Zhi-Chun Lai Associate Professor of Biology and Biochemistry & Molecular Biology 201 Life Sciences Building, University Park, PA 16802 Phone: (814) 863-0479; Lab: 863-3546 Fax: (814) 865-9131 Email: zcl1@psu.edu B.S. in biology, Peking University Ph.D. in molecular genetics, Albert Einstein College of Medicine Lai Lab Web Site

Development of the Drosophila Eye

My laboratory is interested in addressing two fundamental questions in developmental neurobiology: how neurons are specified and how neural tissues are properly patterned. Our experimental system is the Drosophila compound eye. Tools used in our research include genetics, molecular and cell biology.

Photoreceptor Cell Fate Determination

Signaling pathways that involve two receptor tyrosine kinases (Drosophila homolg of EGF receptor and Sevenless) are responsible for transmitting developmental signals to determine cell fates in the eye. However, inhibitory regulation that is required to control cellular competence to respond to inductive signals is less understood. Our research is focused on two nuclear proteins encoded by the yan and tramtrack (ttk) genes. Loss of the yan or ttk function results in the differentiation of ectopic photoreceptors. yan encodes an ETS DNA-binding protein and ttk encodes two zinc-finger proteins. In the presumptive R7 photoreceptor cells, both yan and ttk appear to act antagonistically to the proneural signal mediated by sevenless and Ras1. Moreover, yan and ttk synergistically interact to inhibit the formation of R7 cells. Thus, yan and ttk constitute of a negative nuclear regulatory system that maintains precursor cells in an undifferentiated state until they receive positive signaling, for example, the sevenless-mediated signaling for the development of R7 neuron. An unsolved question is how such inhibitory system is established in precursor cells. To investigate this issue, we are examining yan expression in some mutant background. It is possible that Notch signaling is responsible for the induction of yan expression. We are also currently trying to identify regulatory sequences that can specify yan expression in the developing eye by using a transgenic approach.

Neural Morphogenesis

Construction of a functional organ such as eye requires not only specification of many different cell types, but also proper assembly of these cells in a highly ordered manner. Our preliminary work demonstrated that the delayed furrow (defu) gene can be a critical regulator of eye morphogenesis. Removal of the defu gene activity results in failure of proper spacing between developing unit eyes and coordinated sequences of unit eye assembly. Our ongoing research is aimed at molecular genetic characterization of the defu gene. Future directions of this project include biochemical and evolutionary studies of the defu gene.

Representative Publications:

• Nguyen, D., Rohrbaugh, M. and Lai, Z.-C. 2000. "The Drosophila Homolog of Onecut Homeodomain Proteins is a Neural-specific Transcription Activator with a Potential Role in Regulating Neural Differentiation," Mechanisms of Development, 97: 55-70.
• Wen, Y., Nguyen, D., Li, Y. and Lai, Z.-C. 2000. "The N-terminal BTB/POZ Domain and C-terminal Sequences are Essential for Tramtrack69 to Specify Cell Fate in the Developing Drosophila Eye," Genetics, 156: 195-203.
• Dhulkotia, D., Nguyen, D. and Lai, Z.-C. 2000. "Evolutionary Conservation of a Leucine-Rich Repeat Transmembrane Protein Gp150 in Drosophila and Bombyx," Development Genes & Evolution, 210: 145-150.
• Lai, Z.-C. and Li, Y. 1999. "Tramtrack69 is Positively and Autonomously Required for Drosophila Photoreceptor Development," Genetics, 152: 299-305.
• Price, M. and Lai, Z.-C. 1999. The yan Gene is Highly Conserved in Drosophila and Its Expression Suggests a Complex Role throughout Development," Development Genes & Evolution, 209: 207-217.
• van Huizen, R., Miller, K., Chen, D.-M., Li, Y., Lai, Z.-C., Raab, R.W., Stark, W.S., Shortridge, R.D. and Li, M. 1998. "Two Distantly Positioned PDZ Domains Mediate Multivalent INAD-Phospholipase C Interactions Essential for G Protein-Coupled Signaling," EMBO J., 17: 2285-2297.
• Lai, Z.-C., Fetchko, M. and Li, Y. 1997. "Repression of Drosophila Photoreceptor Cell Fate through Cooperative Action of Two Transcriptional Repressors Yan and Tramtrack," Genetics, 147: 1131-1137.
• S. Li, Y. Li, R. W. Carthew and Z.-C. Lai. 1997. Photoreceptor Cell Differentiation Requires Regulated Proteolysis of the Transcriptional Repressor Tramtrack. Cell 90:469-478.
• K. A. Balczarek, Z.-C. Lai and S. Kumar. 1997. Evolution and Functional Diversification of the Paired Box (Pax)DNA-Binding Domains. Molecular Biology and Evolution 14:829-842.
• Z.-C. Lai, S. Harrison, F. Karim, Y. Li and G.M. Rubin. 1996. Loss of tramtrack gene activity results in ectopic R7 cell formation, even in a sina mutant background. Proc. Natl. Acad. Sci. USA 93:5025-5030.
• S. Kumar, K.A. Balczarek and Z.-C. Lai. 1996. Evolution of the hedgehog gene family. Genetics 142:965-972.
• J.E. Treisman, Z.-C. Lai and G.M. Rubin. 1995. Shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-b responsive gene. Development 121:2835-2845.
• Karim, F., Chang, H., Cutforth, T., Fortini, M., Gaul, U., Lai, Z.-C. , Mardon, G., O'Neill, E., Simon, M., Therrien, M., Wassarman, D., Wolf, T. amd Rubin, G. M. 1994. "Ras and eye development in Drosophila ," Ras, Differentiation and Development. (Ed. Downward, J.; Santos, E.; Martin-Zanca, D.).
• Z.-C. Lai, E. Rushton, M. Bate and G.M. Rubin. 1993. Loss-of-function of the Drosophila zfh-1 gene results in abnormal development of mesodermally derived tissues. Proc. Natl. Acad. Sci. USA 90:4122-4126.
• Z.-C. Lai and G.M. Rubin. 1992. Negative control of photoreceptor development in Drosophila by the product of the yan gene, an ETS domain protein. Cell 70:609-620.
• Lai, Z.-C. , Fortini, M. E. and Rubin, G. M. 1991. "The Embryonic Expression Patterns of zfh-1 and zfh-2, Two Drosophila Genes Encoding Novel Zinc-finger Homeodomain Proteins," Mechanisms of Development 34: 123-134.
• Fortini, M. E., Lai, Z.-C. and Rubin, G. M. 1991. "The Drosophila zfh-1 and zfh-2 Genes Encode Novel Proteins Containing Both Zinc-finger and Homeodomain Motifs," Mechanisms of Development 34: 113-122.

Search the MEDLINE database at PubMed for articles by Z.-C. Lai