Little is known about how neurons recognize and maintain their position. To address these problems, we isolated mutants exhibiting abnormal neuronal positioning (1). In
nj13 mutants, nearly 100% of AFD cell bodies are localized anterior to the nerve ring, while the position of AFD cell body is posterior to the nerve ring in wild type. Also, AIY cell bodies are often mislocalized to the dorsal side. We then asked whether abnormal positioning is general in head neurons and examined the
nj13 animals, in which sensoryneurons and interneurons are labeled with GFP markers. Many neurons are mislocalized anteriorly to the nerve ring, suggesting that the gene mutated in
nj13 is required for proper positioning of head neurons.
nj13 is allelic to
sax-7(
ky146) (2), whose phenotype is indistinguishable from that of
nj13.Cloning with transposon display (3) revealed that
sax-7 encodes a homologue of neural cell adhesion molecule L1, which is a member of the immunoglobulin superfamily and was previously designated LAD-1 (4). We isolated two forms of
sax-7/lad-1 cDNAs: the long form contains six Ig-like domains, five fibronectin type III-like domains, a transmembrane domain, and a cytoplasmic domain, whereas the short form lacks the initial two Ig-like domains of the long form. The expression of the short form in nearly all neurons using
unc-14 promoter completely rescued abnormality in neuronal positioning of
nj13 mutants. In the
nj47 mutant that lacks the first Ig-like domains of the long form and remains the intact short form, neural positioning is completely normal. Thus, the short form is sufficient for neuronal positioning. We also observed that the neuronal position are quite normal in the first larval stage in
nj13 and
ky146 mutants, suggesting that L1 is required for maintenance of neuronal positioning rather than neuronal development (2). Surprisingly, both chemotaxis and thermotaxis are unaffected in
nj13 and
ky146, suggesting that neural network formation is intact. In humans, the patients carrying L1 mutations show a variety of neuronal disorder such as hydrocephalus and mental retardation. Despite the detailed information about these disorders and mutation sites in L1, molecular and cellular bases for L1-caused diseases still remains to be elucidated. We hope that our study will provide molecular and cellular bases of L1 diseases in human. We thank Cori Bargmann for
ky146,Lihsia Chen for sharing information and materials. (1) Sasakura et al (2002). JWMabst (2) Zallen et al (1999). Development 126, 3679. (3) Wicks et al (2000). Dev. Biol. 221, 295. (4) Chen et al (2001). JCB 154, 841.