Peter Okkema, PhD
Professor and Director of Graduate Studies
900 S. Ashland Ave.
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Molecular and genetic control of pharyngeal development and function in C. elegans
The C. elegans pharynx is a rhythmically contracting neuromuscular pump that contracts continuously as the animal feeds. It contains 20 muscles cells and a small nervous system that controls muscle cell contractions. We are interested in how the pharynx forms during embryonic development, and how signals from the pharyngeal neurons control muscle contractions.
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, and the homeodomain transcription factor CEH-28, which controls synapse assembly in one pharyngeal neuron and has a role in regulating pharyngeal muscle contractions.
Conserved transcription factors regulate pharyngeal muscle development in C. elegans
Nematodes do not have a heart or defined circulatory system. However, our studies of transcriptional regulation in the pharyngeal muscles of the nematode C. elegans have revealed developmental similarities with cardiac muscles in other species. Development of the pharyngeal muscles depends on the homeodomain transcription factor CEH-22, the ortholog of the cardiac muscle specification factor Nkx-2.5, and the T-box transcription factor TBX-2, which is the sole C. elegans member of the conserved Tbx2 sub-family of T-box factors.
We currently focus on TBX-2 to understand how T-box factors function. TBX-2 is required for the formation of a subset of pharyngeal muscles, and tbx-2 null mutants exhibit a larval lethal phenotype. Our data indicates that TBX-2 functions as a transcriptional repressor, and that this function depends on modification with the small ubiquitin-like modifier (SUMO). We are currently identifying target genes regulated by TBX-2 and examining how SUMOylation contributes to TBX-2 function. Because many T-box factors contain potential SUMOylation sites, we suggest these may be common mechanisms for controlling T-box factor activity.
Single cell analysis of motor neuron development and function in C. elegans
Control of muscle contraction depends on precise signaling between neurons and their targets, and C. elegans has been used with great success to study many aspects of this signaling. C. elegans has a very simple and well characterized nervous system, and many of the genes controlling synaptic signaling in C. elegans are conserved in humans.
We are using genetic and optical techniques to examine development of a single motor neuron and its communication with target muscles. This neuron called M4 is located in the pharynx, and it stimulates a peristaltic contraction of one pharyngeal muscle type. Our previous work demonstrated that the transcription factor CEH-28 is expressed exclusively in M4, and that ceh-28 mutants exhibit synaptic defects in M4. We are currently identifying target genes regulated by CEH-28 to understand how synapses are appropriately formed in M4, and examining how synaptic defects in ceh-28 mutants affect signaling between M4 and its target muscles.
(Complete list of publications on Google Scholar)
- Ramakrishnan K, Ray P, Okkema PG. (2014). CEH-28 activates dbl-1 expression and TGF-beta signaling in the C. elegans M4 neuron. Developmental Biology 390, 149-159.
- Huber P, Crum T, Clary LM, Ronan T, Packard AV, and Okkema PG. (2013). Function of the C. elegans T-box factor TBX-2 depends on SUMOylation. Cellular and Molecular Life Sciences: CMLS 70, 4157-4168.
- Milton AC, Packard AV, Clary L, Okkema PG. (2013). The NF-Y complex negatively regulates Caenorhabditis elegans tbx-2 expression. Developmental Biology 382(1): 38-47.
- Reinke V, Krause M, Okkema P. (2013). Transcriptional regulation of gene expression in C. elegans. WormBook, 1-34.
- Miller RR and Okkema PG (2011) The Caenorhabditis elegans T-box factor MLS-1 requires Groucho co-repressor interaction for uterine muscle specification. PLoS Genet 7: e1002210.
- Clary LM and Okkema PG. (2010) The EGR family gene egrh-1 functions non-autonomously in the control of oocyte meiotic maturation and ovulation in C. elegans. Development 137(18): 3129-3137.
- Ray P, Schnabel R, Okkema PG. (2008). Behavioral and synaptic defects in C. elegans lacking the NK-2 homeobox gene ceh-28. Developmental Neurobiology 68, 421-33.
- Roy Chowdhuri S, Crum T, Woollard A, Aslam S, Okkema PG. (2006). The T-box factor TBX-2 and the SUMO conjugating enzyme UBC-9 are required for ABa-derived pharyngeal muscle in C. elegans. Developmental Biology 295, 664-77.
PhD, University of Wisconsin, Madison. 1990.
BS, University of Illinois at Urbana-Champaign. 1983.