The
mig-10 gene is necessary for the embryonic migration of neurons CAN, ALM, and HSN as well as development of posterior excretory canals and can encode two isoforms with significant similarity to a family of mammalian Grb signal transduction proteins (1,2). Previously characterized
mig-10 mutations
ct41 and
e2527 cause incomplete embryonic migration of neurons and shortened excretory canals as well as gross phenotypes including a withered tail (Wit), egg-laying defect (Egl) and protruding vulva (Pvl). All of these phenotypes are more severe in
ct41 (an amber mutation expected to truncate severely both MIG-10 isoforms) than
e2527 (a CAG>CAA change in a 3' splice site expected to reduce but not eliminate MIG-10 expression) (2). Recently, a new EMS-induced
mig-10 allele,
ky178, was isolated by Scott Clark and kindly provided to us (S. Clark and C. Bargmann, personal communication). We have sequenced all exons and intron splice sites in
ky178 DNA and have found a change from GT to AT in the absolutely conserved 5' splice site sequence following exon 5. We have also begun a phenotypic characterization of
mig-10(
ky178). The new allele causes gross phenotypes similar to
ct41 and
e2527. To characterize cellular phenotypes, we are using Nomarski optics to score positions of migratory neurons as well as excretory canal anatomy. In addition, we are using a
ceh-23-gfp reporter developed and kindly provided by Jennifer Zallen (3,4) to score position of CAN cell bodies and morphology of CAN axons in all three mutant strains. The new allele resembles
ct41 in causing a fully penetrant truncation of posterior excretory canals anterior to the vulva. In addition,
ky178 appears to affect CAN cell body migration with a penetrance comparable to
ct41. Posteriorly directed CAN axons fail to extend to their normal destinations in the tail in a large fraction of
ky178 individuals; a similar axon phenotype is observed in both
ct41 and
e2527 animals. Anteriorly directed CAN axons are apparently unaffected by all three
mig-10 mutations. The relatively severe phenotypes caused by
ky178 suggest that the new allele may significantly reduce or eliminate
mig-10 function. _______________________________________________________________ 1. Manser, J. and W.B. Wood (1990). Dev. Genet. 11, 49-64. 2. Manser, J. et al. (1997). Dev. Biol. 184, 150-164. 3. Forrester, W. et al. (1998). Genetics 148, 151-165. 4. Forrester, W. and G. Garriga (1997). Development 124, 1831-1843.