Bhagwati Gupta, Ph.D.
Vulval development in Caenorhabditis elegans, Regulation and function of gene networks, Evolution of developmental mechanisms
Specification of cell fate during development involves a large number of genes that interact with each other and are expressed in dynamic patterns. My lab is interested in understanding the function and evolution of gene networks that control cell proliferation and differentiation. Alterations in gene regulation have been shown to give rise to severe developmental abnormalities including hereditary diseases and cancers. Hence, a fundamental understanding of gene regulatory networks is critical for gaining important insights into the pathogenesis of human diseases. Toward this goal, we are studying vulval development in an established model organism,Caenorhabditis elegans and a closely related species, Caenorhabditis briggsae.
- Ranawade et al. (2013) Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/notch-mediated specification of uterine cell fates. G3: Genes, Genomes, Genetics. 3: 1363-1374.
- Salam et al. (2013) A microfluidic phenotype analysis system reveals function of sensory and dopaminergic neuron signaling in C. elegans electrotactic swimming behavior. Worm. 2: e24558.
- Tong J et al. (2013). Microfluidic-based electrotaxis for on-demand quantitative analysis of Caenorhabditis elegans’ locomotion. Journal of Visualized Experiments. 75: e50226
- Sharanya et al. (2012). Genetic control of vulval development in Caenorhabditis briggsae. G3: Genes, Genomes, Genetics.
- Ross et al. (2011). Caenorhabditis briggsae recombinant inbred line genotypes reveal inter-strain incompatibility and the evolution of recombination. PLoS Genetics, 7: e1002174.
- Koboldt et al. (2010). A toolkit for rapid gene mapping in the nematode Caenorhabditis briggsae. BMC Genomics 11:236.
- Seetharaman et al. (2010). Conserved mechanism of Wnt signaling function in vulval cell fate specification in C. elegans and C. briggsae. Developmental Biology 346:128-139.
- Rezai et al. (2010). Electrotaxis of Caenorhabditis elegans in a microfluidic environment. Lab Chip 10:220-226.
- Zhao et al. (2010). New tools for investigating the comparative biology of Caenorhabditis briggsae and Caenorhabditis elegans. Genetics 184:853-863.
- Marri and Gupta (2009). Dissection of lin-11 enhancer regions in Caenorhabditis elegans and other nematodes. Dev. Biol. 325:402-411.
- Haerty et al. (2008). Genome-wide comparative analysis of C. elegans transcription factors reveals conservation of sequence and interaction networks. BMC Genomics 9:399.
- Gupta and Sternberg (2003). The draft genome sequence of the nematode Caenorhabditis briggsae, a companion to C. elegans. Genome biology 4:238.1-238.4.
- Gupta et al. (2003). The C. elegans LIM homeobox gene lin-11 specifies multiple cell fates during vulval development. Development 130:2589-2601.
|Specification of cell fate during development involves a large number of genes that interact with each other and are expressed in dynamic patterns. My lab is interested in understanding the function and evolution of gene networks that control cell proliferation and differentiation.Alterations in gene regulation have been shown to give rise to severe developmental abnormalities including hereditary diseases and cancers. Hence, a fundamental understanding of gene regulatory networks is critical for gaining important insights into the pathogenesis of human diseases. Toward this goal, we are studying vulva development in an established model organism,Caenorhabditis elegans and a closely related species, Caenorhabditis briggsae.
The hermaphrodite vulva provides a unique opportunity to identify genes and study their regulation and function during development. In C. elegans, vulva is formed by the progeny of three out of six multipotential vulval precursor cells (VPCs) that divide three times to give rise to twenty-two cells. The vulval progeny differentiate during L4 larval stage to generate seven different cell types leading to the formation of an adult vulva. The invariant lineage of the VPCs and stereotypic positions of their progeny offer experimental analyses at single-cell resolution.
|lin-11 regulation and pathway in vulval morphogenesis|
|Among the genes regulating vulval morphogenesis, the LIM homeobox family member lin-11 plays a major role. In lin-11 mutant animals, vulval cells fail to acquire correct identities and inappropriately fuse with each other Gupta et.al. Thus, lin-11 confers cell identity by regulating the expression of cell type-specific genes. We are taking a variety of approaches in Genetics, Molecular Biology and Bioinformatics to understand the molecular basis of lin-11 regulation and its downstream targets during vulval morphogenesis.|
|Evolution of gene networks during vulval morphogenesis|
|Comparative studies in metazoan development have revealed that changes in gene regulation play crucial role in evolutionary divergence. In the post-genomic era, bioinformatics and molecular biology tools have facilitated an understanding of some of the gene regulatory networks that have evolved to confer distinct cell fates. To study the molecular basis of developmental differences, we are working on the two closely related Caenorhabditisnematode species, C. briggsae and C. elegans. The genome sequences of these nematodes have been completed thus providing a platform for comparative genomics and biology Gupta and Sternberg. We are utilizing a variety of molecular genetic tools such as RNAi, transgene expression and targeted gene knockouts to understand the network of vulval genes in C. briggsae and their evolutionary differences from C. elegans. The C. briggsae-C. eleganscomparative studies promise to uncover some of the changes in gene networks that specify morphological diversity in animals.|
|Research in the Gupta Lab is currently being funded by the Natural Sciences and Engineering Research Council (NSERC).|