CONTROL OF CLEAVAGE SPINDLE ORIENTATION IN CAENORHABDITIS-ELEGANS - THE ROLE OF THE GENES PAR-2 AND PAR-3

Polarized asymmetric divisions play important roles in the development of plants and animals. The first two embryonic cleavages of Caenorhab ditis elegans provide an opportunity to study the mechanisms controlli ng polarized asymmetric divisions. The first cleavage is unequal, prod ucing daughters with different sizes and fates. The daughter blastomer es divide with different orientations at the second cleavage; the ante rior blastomere divides equally across the long axis of the egg, where as 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 w ith respect to their contribution to the polarity of these divisions. 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. Th e par-2 mutations lead to transverse spindle orientations in both blas tomeres, whereas par-3 mutations lead to longitudinal spindle orientat ions in both blastomeres. The spindle orientation defects correlate wi th defects in centrosome movements during both the first and the secon d 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 th e first cell cycle to affect asymmetric modification of the cytoskelet on. This polar modification leads to different behaviors of centrosome s in the anterior and posterior and leads ultimately to blastomere-spe cific spindle orientations at the second cleavage.