Worm Breeder's Gazette 14(4): 58 (October 1, 1996)

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 egl-20 gene encodes a Wnt protein involved in cell migration and cell polarity

Jennifer Whangbo1, Jeanne Harris2, Gregg Jongeward3, and Cynthia Kenyon1

1 Department of Biochemistry, University of California - San Francisco 94143-0554
2 Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020
3 Department of Biology, University of the Pacific, Stockton, CA 95211

The egl-20 gene functions in diverse aspects of anterior/posterior (A/P) patterning[1]. egl-20(+) activity is required to activate the Hox gene mab-5 in the QL neuroblast and its descendants for proper migration. Independent of mab-5, egl-20 is required to position other migratory cells and to orient certain asymmetric cell divisions along the A/P axis. We mapped egl-20 to a cosmid (W07H7) containing a Wnt gene. We sequenced this Wnt gene from a strong loss-of-function allele and found a mutation that changes a highly conserved cysteine to a serine. We are sequencing the remaining four alleles of egl-20 and attempting to narrow down the rescuing activity to a sub-cloned region of W07H7 containing only the Wnt gene.

Wnt genes define a large family of signaling proteins implicated in many developmental processes including cell proliferation, cell fate determinations, and cell polarity. In Drosophila, a signaling pathway involving the Wnt protein/ wingless, its receptor/frizzled and dishevelled (a novel protein) is required to determine correct planar polarity in adult epidermal cells. In addition to egl-20, other homologs of wingless signaling pathway components have been isolated in C. elegans. For example, lin-44 encodes another Wnt protein[2], lin-17 encodes a frizzled homolog[3] and mig-5 encodes a dishevelled homolog[4]. Like egl-20, lin-17 and mig-5have been implicated in Q cell migration[1,4]. Also, egl-20, lin-44, and lin-17 are known to affect cell polarity[5,6,7].

egl-20, lin-44 and lin-17 function in determining the polarity of certain seam cell lineages. Mutations in the egl-20 gene cause reversals in the polarity of the first V5 cell division [5]. Mutations in lin-17 alone do not affect V5 polarity although they are able to suppress the reversals in egl-20 mutants. lin-44 does not appear to be involved in determining V5 polarity. Mutations in lin-44 lead to polarity reversals in the T cell lineage[6 ]and mutations in lin-17 cause a loss of polarity (symmetric divisions). Sawa and Horvitz have proposed that lin-17/frizzled serves as a receptor for lin-44/wingless . Since lin-44 mutations primarily result in polarity reversals rather than symmetric divisions, they have also proposed that there exists another signal that can affect T cell polarity. We asked if egl-20 is this signal. We found that there was a loss of T cell polarity in the lin-44(n1792); egl-20(n585) double mutant (13/13 animals), as in the lin-17 single mutant. This result suggests that both egl-20 and lin-44 are signals acting through the lin-17 receptor to determine the polarity of the T cell lineage.

The roles of egl-20 and lin-17 in determining V5 polarity and Q cell migration remain unclear. Further molecular analysis of these genes will be informative in understanding how the wingless signaling pathway functions in such seemingly different processes.

1. Harris et al., Development, in press
2. Herman et al., Cell 83:101-110
3. Sawa and Horvitz, 1995 IWM abs.
4. Guo and Hedgecock, 1996 ECWM abs.
5. Whangbo et al., 1996 WCWM abs.
6. Herman and Horvitz, Development 120:1035-1047
7. Sternberg and Horvitz, Dev. Biol.130:67-73