): The pharynx of the nematode Caenorhabditis elegans is a distinct organ consisting of five different cell types, including muscles, neurons, epithelial cells, secretory glands cells and structural cells termed marginal cells. We are interested in how these cells are produced during embryogenesis, and how they are assembled into a functional organ. To address these questions we are focusing on understanding the mechanisms controlling gene expression in one of these cell types, the pharyngeal muscles. While nematodes do not have hearts, the pharyngeal muscles share a number of functional and developmental similarities with cardiac muscle in other species, including humans. We therefore believe that insights gained from this work may have a direct bearing on our understanding cardiac development and function. Pharyngeal muscle gene expression is regulated by a combination of cell type- and organ-specific signals. Factors involved in organ-specific regulation include the winged-helix factor PHA-4 and a novel protein PEB-1, which are both expressed broadly in many pharyngeal cell types. Factors involved in cell type-specific regulation include the homeodomain factor CEH-22 and the basic leucine zipper-related factor ZIP-1, which are expressed more specifically in the pharyngeal muscles. We hypothesize these factors cooperate to regulate pharyngeal muscle development and gene expression. CEH-22 is the earliest known marker of pharyngeal muscle differentiation, and we are currently examining how ceh-22 gene expression is regulated to identify the very early steps specifying pharyngeal muscle fate. We are also investigating how these factors interact with each other to regulate gene expression, and whether these interactions may be conserved in vertebrate heart development. Finally we are specifically examining role the PEB-l plays during pharyngeal development by isolating and characterizing apeb-1 mutant.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Cell Development and Function Integrated Review Group (CDF)
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Greenberg, Judith H
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University of Illinois at Chicago
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Clary, Lynn M; Okkema, Peter G (2010) The EGR family gene egrh-1 functions non-autonomously in the control of oocyte meiotic maturation and ovulation in C. elegans. Development 137:3129-37
Ray, Paramita; Schnabel, Ralf; Okkema, Peter G (2008) Behavioral and synaptic defects in C. elegans lacking the NK-2 homeobox gene ceh-28. Dev Neurobiol 68:421-33
Roy Chowdhuri, Sinchita; Crum, Tanya; Woollard, Alison et al. (2006) 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 295:664-77
Franks, Dawn M; Izumikawa, Tomomi; Kitagawa, Hiroshi et al. (2006) C. elegans pharyngeal morphogenesis requires both de novo synthesis of pyrimidines and synthesis of heparan sulfate proteoglycans. Dev Biol 296:409-20
Okkema, Peter G; Krause, Michael (2005) Transcriptional regulation. WormBook :1-40
Fernandez, Anthony P; Gibbons, Jack; Okkema, Peter G (2004) C. elegans peb-1 mutants exhibit pleiotropic defects in molting, feeding, and morphology. Dev Biol 276:352-66
Vilimas, Tomas; Abraham, Alin; Okkema, Peter G (2004) An early pharyngeal muscle enhancer from the Caenorhabditis elegans ceh-22 gene is targeted by the Forkhead factor PHA-4. Dev Biol 266:388-98
Beaster-Jones, Laura; Okkema, Peter G (2004) DNA binding and in vivo function of C.elegans PEB-1 require a conserved FLYWCH motif. J Mol Biol 339:695-706
Thatcher, J D; Fernandez, A P; Beaster-Jones, L et al. (2001) The Caenorhabditis elegans peb-1 gene encodes a novel DNA-binding protein involved in morphogenesis of the pharynx, vulva, and hindgut. Dev Biol 229:480-93
Thatcher, J D; Haun, C; Okkema, P G (1999) The DAF-3 Smad binds DNA and represses gene expression in the Caenorhabditis elegans pharynx. Development 126:97-107

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