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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
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