Control of Cleavage Spindle Orientation in Caenorhabditis elegans: The Role of the Genes par-2 and par-3

INVESTIGATIONS

Control of Cleavage Spindle Orientation in Caenorhabditis elegans: The Role of the Genes par-2 and par-3

N. N. Cheng, C. M. Kirby and K. J. Kemphues
Present address: Department of Biology, Jordan Hall, Indiana University, Bloomington, IN 47405.

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhabditis elegans provide an opportunity to study the mechanisms controlling polarized asymmetric divisions. The first cleavage is unequal, producing daughters with different sizes and fates. The daughter blastomeres divide with different orientations at the second cleavage; the anterior blastomere divides equally across the long axis of the egg, whereas the posterior blastomere divides unequally along the long axis. We report here the results of our analysis of the genes par-2 and par-3 with respect to their contribution to the polarity of these division. Strong loss-of-function mutations in both genes lead to an equal first cleavage and an altered second cleavage. Interestingly, the mutations exhibit striking gene-specific differences at the second cleavage. The par-2 mutations lead to transverse spindle orientations in both blastomeres, whereas par-3 mutations lead to longitudinal spindle orientations in both blastomeres. The spindle orientation defects correlate with defects in centrosome movements during both the first and the second cell cycle. Temperature shift experiments with par-2(it5ts) indicate that the par-2(+) activity is not required after the two-cell stage. Analysis of double mutants shows that par-3 is epistatic to par-2. We propose a model wherein par-2(+) and par-3(+) act in concert during the first cell cycle to affect asymmetric modification of the cytoskeleton. This polar modification leads to different behaviors of centrosomes in the anterior and posterior and leads ultimately to blastomere-specific spindle orientations at the second cleavage.

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				S. Aono, R. Legouis, W. A. Hoose, and K. J. Kemphues PAR-3 is required for epithelial cell polarity in the distal spermatheca of C. elegans Development, June 15, 2004; 131(12): 2865 - 2874. [Abstract] [Full Text] [PDF]

				M.-F. B. Tsou, A. Hayashi, and L. S. Rose LET-99 opposes G{alpha}/GPR signaling to generate asymmetry for spindle positioning in response to PAR and MES-1/SRC-1 signaling Development, December 1, 2003; 130(23): 5717 - 5730. [Abstract] [Full Text] [PDF]

				J. Nance, E. M. Munro, and J. R. Priess C. elegans PAR-3 and PAR-6 are required for apicobasal asymmetries associated with cell adhesion and gastrulation Development, November 15, 2003; 130(22): 5339 - 5350. [Abstract] [Full Text] [PDF]

				B. Geldmacher-Voss, A. M. Reugels, S. Pauls, and J. A. Campos-Ortega A 90{degrees} rotation of the mitotic spindle changes the orientation of mitoses of zebrafish neuroepithelial cells Development, August 15, 2003; 130(16): 3767 - 3780. [Abstract] [Full Text] [PDF]

				D. G. Srinivasan, R. M. Fisk, H. Xu, and S. van den Heuvel A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C. elegans Genes & Dev., May 15, 2003; 17(10): 1225 - 1239. [Abstract] [Full Text] [PDF]

				A. F. Severson and B. Bowerman Myosin and the PAR proteins polarize microfilament-dependent forces that shape and position mitotic spindles in Caenorhabditis elegans J. Cell Biol., April 14, 2003; 161(1): 21 - 26. [Abstract] [Full Text] [PDF]

				M.-F. B. Tsou, W. Ku, A. Hayashi, and L. S. Rose PAR-dependent and geometry-dependent mechanisms of spindle positioning J. Cell Biol., March 17, 2003; 160(6): 845 - 855. [Abstract] [Full Text] [PDF]

				J. Nance and J. R. Priess Cell polarity and gastrulation in C. elegans Development, March 3, 2003; 129(2): 387 - 397. [Abstract] [Full Text] [PDF]

				M.-F. B. Tsou, A. Hayashi, L. R. DeBella, G. McGrath, and L. S. Rose LET-99 determines spindle position and is asymmetrically enriched in response to PAR polarity cues in C. elegans embryos Development, January 10, 2002; 129(19): 4469 - 4481. [Abstract] [Full Text] [PDF]

				J. A. Kaltschmidt and A. H. Brand Asymmetric cell division: microtubule dynamics and spindle asymmetry J. Cell Sci., January 6, 2002; 115(11): 2257 - 2264. [Abstract] [Full Text] [PDF]

				N. N. Huang, D. E. Mootz, A. J. M. Walhout, M. Vidal, and C. P. Hunter MEX-3 interacting proteins link cell polarity to asymmetric gene expression in Caenorhabditis elegans Development, January 2, 2002; 129(3): 747 - 759. [Abstract] [Full Text] [PDF]

				J.-E. Gomes, S. E. Encalada, K. A. Swan, C. A. Shelton, J. C. Carter, and B. Bowerman The maternal gene spn-4 encodes a predicted RRM protein required for mitotic spindle orientation and cell fate patterning in early C. elegans embryos Development, November 1, 2001; 128(21): 4301 - 4314. [Abstract] [Full Text] [PDF]

				S. Pichler, P. Gonczy, H. Schnabel, A. Pozniakowski, A. Ashford, R. Schnabel, and A. A. Hyman OOC-3, a novel putative transmembrane protein required for establishment of cortical domains and spindle orientation in the P(1) blastomere of C. elegans embryos Development, May 15, 2000; 127(10): 2063 - 2073. [Abstract] [PDF]

				M Nakaya, A Fukui, Y Izumi, K Akimoto, M Asashima, and S Ohno Meiotic maturation induces animal-vegetal asymmetric distribution of aPKC and ASIP/PAR-3 in Xenopus oocytes Development, January 12, 2000; 127(23): 5021 - 5031. [Abstract] [PDF]

				J. Watts, D. Morton, J Bestman, and K. Kemphues The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry Development, January 4, 2000; 127(7): 1467 - 1475. [Abstract] [PDF]

				Y Wei and T Mikawa Formation of the avian primitive streak from spatially restricted blastoderm: evidence for polarized cell division in the elongating streak Development, January 1, 2000; 127(1): 87 - 96. [Abstract] [PDF]

				P. Sadler and D. Shakes Anucleate Caenorhabditis elegans sperm can crawl, fertilize oocytes and direct anterior-posterior polarization of the 1-cell embryo Development, January 1, 2000; 127(2): 355 - 366. [Abstract] [PDF]

				C. A. Rappleye, A. R. Paredez, C. W. Smith, K. L. McDonald, and R. V. Aroian The coronin-like protein POD-1 is required for anterior-posterior axis formation and cellular architecture in the nematode Caenorhabditis elegans Genes & Dev., November 1, 1999; 13(21): 2838 - 2851. [Abstract] [Full Text]

				K. F. O'Connell, C. M. Leys, and J. G. White A Genetic Screen for Temperature-Sensitive Cell-Division Mutants of Caenorhabditis elegans Genetics, July 1, 1998; 149(3): 1303 - 1321. [Abstract] [Full Text] [PDF]

				J. Schumacher, N Ashcroft, P. Donovan, and A Golden A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos Development, January 11, 1998; 125(22): 4391 - 4402. [Abstract] [PDF]

				H. Keating and J. White Centrosome dynamics in early embryos of Caenorhabditis elegans J. Cell Sci., January 10, 1998; 111(20): 3027 - 3033. [Abstract] [PDF]

				L. Rose and K Kemphues The let-99 gene is required for proper spindle orientation during cleavage of the C. elegans embryo Development, January 4, 1998; 125(7): 1337 - 1346. [Abstract] [PDF]

				B. D. Manning, R. Padmanabha, and M. Snyder The Rho-GEF Rom2p Localizes to Sites of Polarized Cell Growth and Participates in Cytoskeletal Functions in Saccharomyces cerevisiae Mol. Biol. Cell, October 1, 1997; 8(10): 1829 - 1844. [Abstract] [Full Text]

				B Bowerman, M. Ingram, and C. Hunter The maternal par genes and the segregation of cell fate specification activities in early Caenorhabditis elegans embryos Development, January 10, 1997; 124(19): 3815 - 3826. [Abstract] [PDF]

				M McGrail and T. Hays The microtubule motor cytoplasmic dynein is required for spindle orientation during germline cell divisions and oocyte differentiation in Drosophila Development, January 6, 1997; 124(12): 2409 - 2419. [Abstract] [PDF]

				L Boyd, S Guo, D Levitan, D. Stinchcomb, and K. Kemphues PAR-2 is asymmetrically distributed and promotes association of P granules and PAR-1 with the cortex in C. elegans embryos Development, January 10, 1996; 122(10): 3075 - 3084. [Abstract] [PDF]

				J. Watts, B Etemad-Moghadam, S Guo, L Boyd, B. Draper, C. Mello, J. Priess, and K. Kemphues par-6, a gene involved in the establishment of asymmetry in early C. elegans embryos, mediates the asymmetric localization of PAR-3 Development, January 10, 1996; 122(10): 3133 - 3140. [Abstract] [PDF]

				K. Mickey, C. Mello, M. Montgomery, A Fire, and J. Priess An inductive interaction in 4-cell stage C. elegans embryos involves APX-1 expression in the signalling cell Development, January 6, 1996; 122(6): 1791 - 1798. [Abstract] [PDF]