The Wnt pathway is a highly conserved signal transduction mechanism. Our interest is to gain more insight into Wnt signaling in general by unearthing the various Wnt pathways that function during C. elegans development. One example of a process of pattern formation that involves Wnt signaling is the development of the seam cell lineage. At hatching, the seam cells form a continuous row in the lateral epidermis of the L1 larva, with the V cells V1-V6 located in the main part of the body. These cells divide once in each larval stage to generate an anterior daughter that fuses with the surrounding hypodermal syncytium and a posterior daughter that becomes a new seam cell. During L2, an additional division occurs that generates two identical seam cell daughters, except in the V5 lineage: V5.p divides asymmetrically to produce a posterior seam cell daughter and an anterior neuroblast daughter that generates the postdeirid sensory sensilium. The potential of V5.p to generate the postdeirid is dependent on intercellular signals delivered by its anterior and posterior neighboring seam cells. During each round of division, contact is lost between the parent seam cells and later reformed between the daughter cells. For V5.p to give rise to the postdeirid, it must contact its neighbors within a certain time frame (1). The intercellular signaling that occurs upon contact inhibits the expression of the Hox gene
mab-5 in V5.p (2). If contact formation between V5.p and its neighbors is prevented,
mab-5 is activated in V5.p and no postdeirid is formed. This effect is reduced in
egl-20/Wnt,
lin-17/Fz and
bar-1/-catenin mutants, suggesting that a canonical Wnt signaling mechanism is required for the ectopic activation of
mab-5 in V5.p. In the wild-type situation, the signals that V5.p receives from neighboring seam cells may function to inhibit this Wnt pathway. To identify (inhibitory) components of this Wnt signaling pathway, a mutagenesis screen was performed to generate mutants that are defective in postdeirid formation. For the easy recognition of such mutants, a transgenic line expressing gfp controlled by the
dat-1 promoter region was used.
dat-1 encodes a dopamine transporter that is expressed in the postdeirid neuron PDE as well as in three pairs of head neurons in the adult worm. Several mutants were isolated that are currently being analyzed. (1) Judith Austin and Cynthia Kenyon, Development 120, 313-324; (2) Craig P. Hunter, Jeanne M. Harris, Julin N. Maloof and Cynthia Kenyon, Development 126, 805-814