Worm Breeder's Gazette 17(2): 33 (April 1, 2002)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

atp-2 Controls Development in a Cell Nonautonomous Manner

William Y. Tsang, Bernard D. Lemire

Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.

The growth and development of an organism are energy-dependent and rely on the mitochondrial respiratory chain (MRC) as the major source of ATP. The MRC is made up of 5 protein complexes, and its biogenesis requires the coordinate expression of genes from both the nuclear and the mitochondrial genomes. A defective MRC has been implicated in a wide variety of human diseases including diabetes, myopathies, neuromuscular and heart diseases.

We are developing the nematode, Caenorhabditis elegans as a model system for studying mitochondrial diseases. We have previously isolated a MRC mutation in the atp-2 gene encoding the active site ß subunit of the ATP synthase. The ua2 mutation is a deletion and is homozygous lethal: atp-2(ua2) animals hatch and develop through 2 larval stages before arresting at the L3 stage.

We are performing mosaic analysis to determine whether losses of the wild type atp-2 gene in certain cells or tissues can prevent development beyond the L3 stage. We have generated several strains of the genotype atp-2(ua2); svDp1{sDp3[atp-2(+)]-svEx12[unc-4(+)-sur-5::gfp]} (svDp1 is a gift from Dr. S. Tuck). Mosaic animals are identified by screening plates for candidates with less intense fluorescence as observed in the dissecting microscope. They are then examined with the compound microscope to identify the exact nature of their losses. We have mainly focused on early duplication losses (i.e. losses in the AB, ABa, ABp, P1, P2, EMS, E, MS, C, and D(P3) lineages; the sur5::gfp reporter is not expressed in the germ line, which is derived from P3). Animals with a loss in one or more of the AB, ABp, P1, P2, EMS, MS, C and D(P3) precursor cell all arrest at L3, whereas a loss in either ABa or E gives rise to both L3 arrested and L4/adult worms. Our data suggests that atp-2 controls development cell nonautonomously and may be involved in the production or the regulation of a global, developmental signal required for the L3-to-L4 transition.