Control of cell type-specific gene expression and organogenesis in C. elegans
As an animal develops from a fertilized egg to a new born, an incredible variety of cell types are differentiated and organized into distinct tissues and organs. This organization is reproducible between individuals within a species, and defects in it can lead to deformities or inviability. How are these processes controlled? What ensures that appropriate cell types are present to form a functional organ? How are very different cell types incorporated into a single organ?
Our laboratory studies the processes of cell differentiation and organogenesis in the nematode Caenorhabditis elegans
. C. elegans
is one of the simplest and best characterized multi-cellular animals, and it is increasingly used as a 'model organism' to study animal development. Many of the developmental mechanisms identified in C. elegans are conserved in more complex animals including humans, and we hope our work in C. elegans will contribute to a broader understanding of biology.
We have focused on understanding the development of the C. elegans
pharynx, an organ that makes up an essential part of the digestive system. The pharynx consists of several different cell types, including muscles, neurons, epithelial cells, and secretory glands. We are interested in how these very different cells are produced, and how they become arranged into a functional organ during the embryonic development of the worm.
To explore these questions, we have focused on understanding the development of one pharyngeal cell type, the muscles. C. elegans
pharyngeal muscle shares a number of functional and developmental characteristics with cardiac muscle in other species, and we therefore believe it provides an excellent system to examine both conserved mechanisms controlling muscle formation, as well as the general processes of cell-type specification and organogenesis.
We have found that pharyngeal muscle development is controlled by a combination of signals that promote cell type differentiation and organogenesis. Cell type-specific signals involve a transcription factor called CEH-22, which is related to factors regulating heart development in other animal types. Organ-specific signals involve a number of different factors that have been identified by our lab and others interested in pharyngeal development. We are examining the role each of these factors in pharyngeal development to better understand the processes of cell differentiation and organogenesis.
Milton, A.C., Packard, A.V., Clary, L., and Okkema, P.G. (2013). The NF-Y complex negatively regulates Caenorhabditis elegans tbx-2
expression. Dev Biol
Huber, P., Crum, T., Clary, L.M., Ronan, T., Packard, A.V., and Okkema, P.G. (2013). Function of the C. elegans
T-box factor TBX-2 depends on SUMOylation. Cellular and
Molecular Life Sciences : CMLS. [epub ahead of print
Reinke, V., Krause, M., and 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, L. M. and Okkema, P. 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(18): 3129-3137.
Ray, P., Schnabel, R. and Okkema, P. G. (2008). Behavioral and synaptic defects in C. elegans
lacking the NK-2 homeobox gene ceh-28. Dev Neurobiol 68, 421-33.
Roy Chowdhuri, S., Crum, T., Woollard, A., Aslam, S. and Okkema, P. G. (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.