Worm Breeder's Gazette 12(3): 102 (June 15, 1992)
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.
The homeobox-containing mec-3 gene of C. elegans is expressed in ten mechanosensory neurons and is necessary for these cells to acquire their fate. All the mec-3 -expressingcells are anterior daughters from an asymmetric cell division. To understand how this occurs, we have examined expression of a mec-3 -/lacZfusion in various mutant backgrounds. Three lines of evidence support the idea that asymmetric expression of mec-3 derives from an asymmetry in the parent cell that divides to give a mec-3 -expressingdaughter, and not from an interaction between the two daughter cells.
To explain why mec-3 is always expressed in an anterior daughter cell, several models can be envisioned. According to the first model, two cells of equal potential are generated by an intrinsically symmetric division. The positions of the cells are slightly different, so that one is closer to a local signal that influences it to express certain proteins that differentiate it from the other cell. By the second model [See Figure 2], the division of the parent cell is intrinsically symmetric and produces two cells that can sense a morphogen that is present in a gradient in the animal. According to the level of sensation, an internal cue accumulates in parent cell until it reaches some threshold, at which point the cell becomes committed to one fate and commands its sister to take on a distinct fate. According to the third model, the parent cell has an asymmetric distribution of some factor, so that when the cell divides, one cell receives the factor and the other does not The asymmetry in the parent cell could arise in response to a gradient of a morphogen [See Figure 3] or in response to oriented cues in the extracellular matrix [See Figure 4].
The first model [See Fi gure1 ]is unlikely, based on the fact that the divisions that generate mec-3 -expressingcells occur at various times and places, and yet this cell is always an anterior daughter. Also, in a lin-22 mutant, the lineage that gives rise to the mec-3 -expressingPVD cell is repeated several times along the anterior posterior axis of the animal, and always occurs in the normal pattern. We therefore ignore model 1 [See Figure 1], and concentrate on distinguishing models 2 and 3 [See Figures 2-4]. Model 2 has some precedence in Drosophila: in the bristle lineage, Notch is require for the hair cell and the socket cell, which are sisters, to acquire different fates.
Several lines of evidence support the second model over the third. In a lin-12 glp-1 double mutant, mec-3 is still expressed in the correct set of cells. When progeny of a lin-12 glp 1/ dpy-17 , mec-3 -lacZstrain are stained with Xgal, one can easily identify arrested L1 s with the characteristic bent nose and bulging anus that express the mec-3 -lacZfusion in the FLP, ALM, and PLM cells. As far as we know, lin-12 and/or glp 1 is necessary for every known cell fate decision in which two cells compete for the same fate. This observation therefore argues against model 2 [See Figure 2] (with the caveat that there might exist some additional, unsuspected system for distinguishing between cells competing for the same fate.
In addition, lin-17 is necessary for constraining mec-3 expression to the correct cells. In a lin-17 ( n671 )mutant, additional mec-3 -expressingcells can be seen: on average, about .3-1 additional cells can be seen per animal observed. We assume that such extra cells arise by sister-sister cell fate transformations, as described by Sternberg and Horvitz (Dev. Biol. 130, 67-73.) Such transformations can occur at the final cell division, or at preceding divisions: for the right post-deirid to have five cells, two of which express mec-3 ,the sister of the mec-3 -expressingPVD cells (which normally dies) must be converted into PVD; sister-sister transformations earlier in the lineage with give only four cells in this group, or a duplication of the entire group. Both types of animals are seen. Since in other contexts, lin-17 appears to be necessary to generate an asymmetry asymmetry that exists in the parent cell, these results also support model 3.
In lin-5 mutants, post-embryonic cell division is blocked, but DNA replication still occurs, so that post-embryonic blast cells become polyploid. In this mutant, the O cells, which normally give rise to mec-3 -expressingdaughters. instead become polyploid and express mec-3 .This would be expected according to model 3[See Figure 3 & 4], but is somewhat more to explain with model 2 [See Figure 2], as in the lin-5 mutant, there can be no sister-sister interaction, as the mec-3 -expressingcell does not have a sister in the usual sense. By itself, this result does not rule out model 2 [See Figure 2] (one could say that expressing mec-3 is the primary fate of the O daughters), but we imagine this situation is similar to that for the P cells in a lin-5 mutant. Albertson et al. (Dev. Biol. 63: 165-178) showed that these cells do not divide, but instead appear to express the differentiated characteristics of all of their daughters. According to this idea, such a cell might express a collection of regulatory genes, analogous to mec-3 ,that would be expressed in their various daughter cells. This would be consistent with the idea that expression of such regulatory genes is driven by cell-intrinsic mechanisms, and that an interaction with the outside of the cell is necessary to determine how regulatory factors are distributed into different daughter cells.
We also examined the pattern of mec-3 expression in other mutants, including mab-5 , mig-1 , lin-44 , unc-11 , unc-53 , egl-27 ,and unc-73 .An unc-73 ( e936 )strain also shows mec-3 expression in extra cells, though much less frequently than in lin-17 ( n671 ).In addition, unc-73 ( e936 )shows an alteration in PVM migration, occasional extra vulva blips, and changes in PLM process position, phenotypes shared with lin-17 ( n671 ).
Albertson et al. Dev. Biol. 63: 165-178
