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Biological Sciences Department Faculty
Ph.D., Massachusetts Institute of Technology (M.I.T.), 1990
I am interested the process by which cells form specialized attachments to neighboring
tissues during growth and development. These attachments are crucial for organismal
morphology and a wide variety of functions including the transmission of mechanical
force between adjacent tissues. Attachment failure can result in birth defects and
a variety of known human diseases.
Inmy laboratory we are studying the regulation of cell attachments in the muscle system
of the nematode Caenorhabditis elegans, a simple invertebrate. We have identified a number of genes involved in regulating
cell attachment in response to growth and are examining their specific roles.
Every living organism has a characteristic form. In simple unicellular organisms such as bacteria or yeast this form is the same as the form of the cell. In multicellular organisms such as worms or ourselves this form emerges from the shape of individual cells and the geometry of their assembly into a mechanically coupled structure. The coupling of cells together depends on the formation of attachments between adjacent cells, or between cells and surrounding non-cellular matrices during development and is critical to proper tissue assembly and morphogenesis. In adults these attachments ensure tissue integrity, body architecture, and the transmission of mechanical force between adjacent tissues. In my lab we study the formation and maintenance of cell attachment between the epidermis and surrounding tissues in the nematode Caenorhabditis elegans. Normal locomotion in this simple invertebrate requires transmission of contractile force from the skeletal muscles to the exoskeleton (cuticle) via a series of cell-matrix and cell-cell linkages. Mutations in genes required for the development, regulation, or maintenance of these linkages can be isolated by identifying mutant animals that show a flaccid paralysis due to the failure of the mechanical links.
Todate, 11 genes have been identified that are required for the integrity of attachments between the muscle and cuticle during postembryonic growth and have been designated mua, for muscle attachment defective. Three have been cloned. MUA-5 is a novel membrane anchored matrix protein that localizes to hemidesmosomes in the epidermis and is required for attachment between the epidermis and the exoskeleton. MUA-6 is an intermediate filament protein that also localizes to these same attachment structures and is required for the structural integrity of the epidermis itself. Interestingly, MUA-3 and MUA-6 appear to interact in vivo. Finally, MUA-1 is a putative zinc-finger transcription factor that is expressed in the epidermis throughout development. Other mua genes also appear to be acting within the epidermis. In animals mutant for mua-2, mua-5, or mua-10, the primary defect also appears to involve the hypodermal hemidesmosomes or their associated intermediate filaments. Thus, these three genes are predicted to encode proteins that are part of the epidermal hemidesmosome/IF complexes and required for the normal development of these structures.
Weare currently examining tissue and ultra-structural changes in mua-1, mua-2, mua-5, and mua-10, using fluorescent probes and electron microscopy, cloning mua-2, mua-5, and mua-10, and extending our studies of MUA-1 function. In addition we are using genetic reversion screens to identify other genes that interact with the mua-6, and RNA interference to examine the role in C. elegans of genes identified by homology to vertebrates as encoding proteins found at attachment structures.
Xiao, H.; V. Hapiak; K. Smith, L. Lin; R. Hobson, J. Plenefisch; R. Komuniecki, (2006) SER-1, a Caenorhabditis elegans 5-HT(2)-like receptor, and a multi-PDZ domain containing protein (MPZ-1) interact in vulval muscle to facilitate serotonin-stimulated egg-laying. Dev. Biol. 298:379-91
V.Hapiak, M. C. Hresko, L. A, Schriefer, K. Saiyasisongkhram, M. Bercher and J. Plenefisch (2003) mua-6, a Gene Required for Tissue Integrity in C. elegans, Encodes a Cytoplasmic Intermediate Filament Dev. Biol. 263:330-342
Bercher, M, J. Wahl, B. E. Vogel, C. Lu, E. M. Hedgecock, D.H.Hall, and J.D. Plenefisch (2001) mua-3, a gene required for mechanical tissue integrity in Caenorhabditis elegans, encodes a novel transmembrane protein of epithelial attachment complexes J. Cell. Biol. 154:415-426
Geng J, Plenefisch J, Komuniecki PR, Komuniecki R. (2002) Secretion of a novel developmentally regulated chitinase (family 19 glycosyl hydrolase) into the perivitelline fluid of the parasitic nematode, Ascaris suum. Mol Biochem Parasitol. 124:11-21.
Hapiak, V, M. C. Hresko, L. A. Schriefer, K. Saiyasisongkhram, M. Bercher and J. Plenefisch (2003) mua-6, a Gene Required for Tissue Integrity in Caenorhabditis elegans, Encodes a Cytoplasmic Intermediate Filament. Dev. Biol. 263:330-342
Plenefisch, J.D. , X. Zhu, and E. M. Hedgecock (2000) Fragile Skeletal Muscle Attachments in Dystrophic Mutants of Caenorhabditis elegans: Isolation and Characterization of the mua Genes Development 127, 1197-1207
Plenefisch, J., H. Xiao, B. Mei, J. Geng, P. R. Komunieki, R. Komunieki (2000) Secretion of a novel class of iFABPs in Nematodes: coordinate use of the Ascaris/Caenorhabditis model systems. Molec. Bioch. Parasit. 105, 223-236
H.Hutter, B. E. Vogel, J. D. Plenefisch, C. R. Norris, R. B. Proenca, J. Spieth, C. Guo, S. Mastwal, X. Zhu, J. Scheel, and E. M. Hedgecock (2000) Conservation and Novelty in the Evolution of Cell Adhesion and Extracellular Matrix Genes. Science 287, 989-994
DeLong, L., J. D. Plenefisch, R. D. Klein, and B. J. Meyer (1993) Feedback control of sex determination by dosage compensation revealed through Caenorhabditis elegans sdc-3 mutations. Genetics 133, 875- 896
Plenefisch, J. D., L. DeLong, and B. J. Meyer (1989) Genes that implement the hermaphrodite mode of dosage compensation in Caenorhabditis elegans. Genetics 121, 57-76
Miller, L. M., J. D. Plenefisch, L. P. Casson, and B. J. Meyer (1988) xol-1: a gene that controls the male modes of both sex determination and X chromosome dosage compensation in C. elegans. Cell 55, 167-183