The major interest of my lab is the understanding of the molecular events that determine various aspects of animal development. We use the nematode Caenorhabditis elegans as a model system and our research combines genetic, molecular biological, and cell biological approaches as well as advanced imaging technology.
Our current research focuses on the following two areas:
1. Regulation of anterior-posterior polarity and cell fate determination during embryogenesis.
The anterior-posterior polarity of C. elegans embryos is established at fertilization. The polarity information is transmitted from division to division such that cells born during embryogenesis remain aware of their position with respect to the polarity of the entire embryo. We have shown that a transcription factor, POP-1, plays an important role in a-p polarity during embryogenesis. At each a-p division, the two daughter cells have different nuclear POP-1 levels and this POP-1 asymmetry is regulated by a conserved Wnt/MAP kinase signaling pathway. We have recently demonstrated that POP-1 levels are lowered in the signal-receiving cell, whereas levels of a coactivator beta-catenin are increased in response to signal, and that this change in POP-1 to beta-catenin ratio converts POP-1 from a repressor to an activator of Wnt target genes. We are further characterizing the cue(s) which provides the anterior-posterior information in the fertilized embryo, the signaling transduction pathway that transmits this cue to POP-1, the molecular mechanism(s) that result in asymmetric levels of POP-1 protein in anterior versus posterior sister cells, and the molecular consequences of POP-1-mediated transcriptional activation.
2. Genetic and molecular characterization of the oocyte to embryo transition.
We have identified two genes, oma-1 and oma-2, that encode closely-related zinc finger proteins redundantly required for oocyte maturation and characterized C. elegans mutants defective in these two genes. The OMA proteins are expressed exclusively in the female germline and in the newly fertilized embryo, but are degraded rapidly soon after the first mitotic division. A gain-of-function oma-1 mutant which is not properly degraded results in embryonic lethality. We are investigating how OMA-1 and OMA-2 regulate oocyte maturation and their function(s) in early embryonic development. We have recently identified a function for OMA-1 and OMA-2 in global repression of transcription in early germcell precursors. This repression is by a novel mechanism, whereby the OMA proteins interact with, and sequester to the cytoplasm, the critical TFIID component TAF-4, thereby inhibiting the formation of functional transcription preinitiation complexes in the nucleus. OMA proteins have also been implicated in RNA-binding and translational control. The OMA proteins therefore are multifunctional proteins that play several pivotal roles in the transition from quiescent oocyte to metabolically dynamic embryo. We are identifying domains and modifications that underlie the complex regulation, interaction and function of the OMA proteins.
RESEARCH INTERESTS
cell fate determination
anterior-posterior polarity
oocyte maturation
oocyte-to-embryo transition
RECENT PUBLICATIONS
Guven-Ozkan, T., Nishi, Y., Robertson, S.M., and Lin, R, "Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TFIID component TAF-4" Cell, 135:149-160, 2008
Nishi, Y., Rogers, E., Robertson, S.M., and Lin, R., "Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6" Development, 135:687-697, 2008
Huang, S., Shetty, P., Robertson, S.M., and Lin, R., "Binary cell fate specification during C. elegans embryogenesis driven by reiterated reciprocal asymmetry of TCF POP-1 and its coactivator beta-catenin SYS-1" Development, 134:2685-2695, 2007
Shetty, P., M-C. Lo, S.M. Robertson and R. Lin, "C. elegans TCF protein, POP-1, converts from repressor to activator as a result of Wnt-induced lowering of nuclear levels." Dev. Biol., 285:584-592, 2005
Lo, M-C., Gay, F., Odom, R., Shi, Y., and Lin, R., "A 14-3-3 protein, PAR-5, mediates nuclear export of POP-1 in Wnt/MAP kinase responsive cells in C. elegans embryos" Cell, 117:95-106, 2004
SIGNIFICANT PUBLICATIONS
Guven-Ozkan, T., Nishi, Y., Robertson, S.M., and Lin, R, "Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TFIID component TAF-4" Cell, 135:149-160, 2008
Lo, M-C., Gay, F., Odom, R., Shi, Y., and Lin, R., "A 14-3-3 protein, PAR-5, mediates nuclear export of POP-1 in Wnt/MAP kinase responsive cells in C. elegans embryos" Cell, 117:95-106, 2004
Detwiler, M., Reuben, M.R., Li, X., Rogers, E., and Lin, R., "Two zinc finger proteins, OMA-1 and OMA-2, are redundantly required for oocyte maturation in C. elegans." Dev. Cell, 1:187-199, 2001
Lin, R., R. Hill, and J. R. Priess, "POP-1 and anterior-posterior fate decisions in C. elegans embryos." Cell, 92:229-239, 1997
Lin, R., Thompson, S and Priess, J.R., "POP-1 encodes an HMG box protein required for the specification of a mesoderm precursor in early C. elegans embryos" Cell, 83:599-609, 1995
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