Department of Molecular and Cellular Biology
Molecular and Cellular Biology
16 Divinity Avenue, BL 3015
Cambridge, MA 02138
The Mango lab studies organ development using a simple organ, the C. elegans foregut, that nonetheless faces the same hurdles that confront organs in more complex animals. We combine molecular genetics, genomics, cell biological and most recently modeling approaches to address three aspects of organogenesis:
Pluripotency and embryogenesis (see 1): Cells from early embryos are pluripotent, meaning they can adopt any cell fate. Over time, cells lose pluripotency and acquire a defined fate such as ‘foregut’. We have begun to explore the mechanisms that govern pluripotency and its loss in a developing embryo. Embryos have both common and unique characteristics for developmental plasticity, compared to in vitro systems such as ES cells. We are particularly interested in the contribution of nuclear organization, chromatin architecture and transcriptional circuitry.
Transcriptional pathways for organ development (see 2): The FoxA family of transcription factors establishes the foregut in all animals that have been examined, but the mechanisms are not well understood. In one project, we are studying how C. elegans PHA-4/FoxA controls transcription within a developing organ, including the role of DNA binding affinity for temporal control. In another project, we have discovered a cohort of novel but conserved genes that may be negative regulators of pha-4/FoxA. One of these conserved factors is amplified in certain cancers, suggesting a possible link to human disease. Our continuing goal is to elucidate what these novel factors do in C. elegans and vertebrates.
Environmental Cues (see 3). More recently, we have extended our studies to probe how the developmental pathways that govern gut development in embryos respond to environmental cues. This project has lead us to investigate the influence of the nervous system on gut development, and mechanisms of trans-generational signaling, whereby cues from the parent or grand-parent shape the development of their offspring.
T. Yuzyuk, T. Fakhouri, J. Kiefer and S. E. Mango. The Polycomb Complex Protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos. Developmental Cell, 16(5) 699-710 (2009).
Meister, P., S.E. Mango and S.M. Gasser. Locking the genome: nuclear organization and cell fate. Curr. Opin. Genetics & Dev, 21: 167-174 (2011).
J. Gaudet, and S.E. Mango. Regulation of Organogenesis by the Caenorhabditis elegans FoxA Protein PHA-4. Science 295: 821-825 (2002).
Fakhouri, T., J. Stevenson, A.D. Chisholm and S.E. Mango. Dynamic chromatin organization during foregut development mediated by the organ selector gene PHA-4FoxA. PLoS Genetics, 12;6(8):e1001060 (2010). PMCID: PMC2920861
K. Sheaffer, D.L. Updike and S.E. Mango. The Target of Rapamycin (TOR) pathway antagonizes pha-4/FoxA to control development and aging. Current Biology, 18(18):1355-64 (2008).
Ao W, Gaudet J., Kent W.J., Muttumu S., and Mango S.E. Environmentally Induced Foregut Remodeling by PHA-4/FoxA and DAF-12/NHR. Science, 305:1743-6 (2004).
For a complete listing of publications click here.
Last Update: 7/26/2012