Organs are complex structures usually consisting of a variety of highly differentiated cell types that work together to carry out specific functions.  Defects in the development or the function of an organ can have a profound effects, and  such defects underlie a variety of human congenital diseases [1].  Our laboratory is examining the genetic and molecular mechanisms controlling organ formation, and those controlling organ function using the pharynx of the nematode Caenorhabditis elegans as a simple model system.

The pharynx is an ideal system to address these issues.  It is a prominent neuromuscular tube located at the anterior of the digestive system that functions as a rhythmically contracting pump to ingest and macerate bacteria during feeding.  The pharynx consists of muscles and a variety of other cell types, and it contains a small nervous system that controls pharyngeal muscle contractions [2, 3].  The pharynx is a wonderful model for both developmental studies [4], and studies of how nervous systems control behavior [5].

We are currently examining the function of phylogenetically conserved transcription factors that control pharyngeal muscle development and the behavior of the pharynx.  These factors include the T-box transcription factor TBX-2, which is essential for the development of muscles in the anterior half of the pharynx [6, 7], and the homeodomain transcription factor CEH-28, which controls synapse assembly in one pharyngeal neuron and has a role in regulating pharyngeal behavior (Ray et al., in press).  In addition, we are asking if molecular mechanisms by which TBX-2 regulates target genes are similarly used by additional T-box factors in C. elegans and other organisms.  Our current and future goals include:

• characterizing the position of tbx-2 in the pathway controlling anterior pharyngeal muscle development
• determining the role of protein SUMOylation and interaction with Groucho family co-repressors in TBX-2 function
• determining if SUMOylation and Groucho interaction are conserved features of T-box proteins in C. elegans and mammals
• characterizing the role of CEH-28 in synapse assembly and function of the M4 pharyngeal motorneuron. 

References:

1.            Buyse, M.L., ed. Birth defects encyclopedia: the comprehensive, systematic, illustrated reference source for the diagnosis, delineation, etiology, biodynamics, occurrence, prevention, and treatment of human anomalies of clinical relevance. 1990, Center for Birth Defects Information Services: Dover, MA, U.S.A. 1892.
2.            Albertson, D.G. and J.N. Thomson, The pharynx of Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci, 1976. 275(938): p. 299-325.
3.            Sulston, J.E., et al., The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev Biol, 1983. 100(1): p. 64-119.
4.            Mango, S.E., The C. elegans pharynx: a model for organogenesis (January 22, 2007), in WormBook, T.C.e.R. Community, Editor. 2007, WormBook, doi/10.1895/wormbook.1.129.1.
5.            Franks, C.J., et al., Anatomy, physiology and pharmacology of Caenorhabditis elegans pharynx: a model to define gene function in a simple neural system. Invert Neurosci, 2006. 6(3): p. 105-22.
6.            Roy Chowdhuri, S., et al., The T-box factor TBX-2 and the SUMO conjugating enzyme UBC-9 are required for ABa-derived pharyngeal muscle in C. elegans. Dev Biol, 2006. 295(2): p. 664-77.
7.            Smith, P.A. and S.E. Mango, Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans. Dev Biol, 2007. 302(1): p. 25-39.