A/P patterning in C. elegans larvae requires position-specific expression of the Hox genes
lin-39,
mab-5 and
egl-5 as well as combinatorial interactions between these Hox proteins where their expression domains overlap. Several phenotypes of
egl-27 mutants indicate that
egl-27 plays roles in the control of Hox gene expression and Hox protein activity. Some of these phenotypes and the cells affected are described below. Q/V5 Division: Near the end of embryogenesis, there are 10 seam cells on each side of the worm. Of these 10 cells, Q/V5 is the only cell to divide just before hatching. It gives rise to Q, our favorite migratory neuroblast, and V5, a seam cell. This Q/V5 division fails to occur about half the time in
egl-27 mutant animals. QL Migrations: Even when Q/V5 on the left divides in
egl-27 animals to give rise to QL, QL's descendants sometimes fail to migrate posteriorly. Genetic epistasis and expressions studies of MAB-5 indicate that this is due to reduced or no MAB-5 expression in the QL lineage. Pn.p Fusions with
hyp7 in Hermaphrodites: Fusions of P(1-11).p cell are controlled by
lin-39; LIN-39 is normally expressed in P(3-8).p during L1-L3 which keeps these cells unfused. In
egl-27 mutant hermaphrodites, P(3-8).p are unfused but P(9-11).p often remain unfused as well because LIN-39 is sometimes ectopically expressed in P(9-11).p. Surprisingly, in the
lin-39;
egl-27 double mutant, P(4-11).p stay unfused at lower frequencies, indicating that
egl-27 may regulate additional factor(s) that can control Pn.p cell fusions. Pn.p Fusions with
hyp7 in Males: Fusions of P(1-11).p are governed combinatorially by
lin-39 and
mab-5. Pn.p cells lacking both LIN-39 or MAB-5 will fuse with
hyp7. Either LIN-39 or MAB-5 alone keeps a Pn.p cell unfused. However, when both LIN-39 and MAB-5 are present in the same Pn.p cell, their activities somehow cancel out and the Pn.p cell fuses. In
egl-27 mutant males, Pn.p cells expressing both MAB-5 and LIN-39 still remain unfused, indicating that they are unable to integrate signals from MAB-5 and LIN-39 during the fusion decision. Pn.a Cell Migrations:
lin-39(+) prevents the P(3-8).a cells from migrating anteriorly. LIN-39 is not normally expressed in P(1-2).a, hence these cells migrate anteriorly. In
egl-27 animals, P(1-4).a migrate anteriorly, revealing a new boundary within the
lin-39 domain. Surprisingly, LIN-39 expression in P(3-4).a is indistinguishable from wild type animals, suggesting that P(3-4).a require both EGL-27 and LIN-39 to remain stationary. Other phenotypes of
egl-27 animals include defects in several cell migrations as previously described by the Horvitz and Hedgecock Labs.
egl-27 also specifies proper T cell polarity and its resembles Mta-1, a novel gene found to be overexpressed in metastatic vs. non-metastatic human tumor cell lines (M. Herman, pers. comm.; see Herman et al., 1998 Mid-West Worm Meeting abstract). Since
egl-27 defines an unfamiliar gene implicated in many processes, we are curious as to whether its pleiotrophic phenotypes will lead to some unifying hypothesis about its function, or whether it acts to control different fates in different cell types.