Toll is a conserved cell-surface receptor that plays two major roles in Drosophila: in dorso-ventral patterning in the early embryo and in anti-microbial innate immunity (1). Many of the vertebrate homologues of Toll, the Toll-Like Receptors or TLRs, are known to be involved in innate immunity. In contrast to both insects and vertebrates, the nematode C. elegans possesses just one TLR, TOL-1, essential for early development (2). Through 4D Nomarski microscropy analyses carried out in A. Chisholms lab (UCSD), we have found that in
tol-1 null mutants both the closure of the gastrulation cleft and epidermal ventral closure are abnormal. In vitro, Toll has been shown to function as a cell-adhesion molecule (3). Our results suggest a role for TOL-1 in the adhesion or migration of epidermal cells in vivo. We are undertaking genetic screens for suppressors of the
tol-1 phenotype in the hope of identifying novel genetics partner for TOL-1, as well as directly testing its role in cell adhesion. Unlike Toll,
tol-1 appears not to play a direct role in nematode defence against infection. On the other hand, adult worms have a tendency to avoid the bacterial pathogen Serratia marcescens and TOL-1 is necessary for this behaviour (2). We have found that this behaviour varies as a function of the worms age and population density, suggesting that it includes contributions both from the bacteria and the worms themselves. We are currently testing worm with defects either in sensory behaviours (e.g.
glr-1,
nmr-1) or in secretion (e.g.
daf-22) to see whether we can identify mutants that phenocopy the
tol-1 repulsion defect. Preliminary tests that oppose attraction to diacetyl and avoidance of copper (4), also suggest that
tol-1 might play a more general role in sensory integration. 1. M. P. Belvin, K. V. Anderson, Annu Rev Cell Dev Biol 12, 393-416 (1996). 2. N. Pujol et al., Curr Biol 11, 809-21 (2001). 3. F. J. Keith, N. J. Gay, Embo J 9, 4299-306. (1990). 4. T. Ishihara et al., Cell 109, 639-49 (2002).