Xerl, a novel CNS-specific secretory protein, establishes the boundary between neural plate and neural crest

A novel gene, Xerl, has been found as a CNS-specific gene encoding a secretory protein. In order to clarify a function of Xerl, we first examined Xerl-expressing areas during early development. Comparison with XlSox-2-positive neural plate and ADAM13-positive neural crest showed that Xerl expression was limited within the neural plate area. Microinjection of Xerl mRNA into 2- or 4-cell stage embryos indicated that Xerl overexpression caused the regional expansion of XlSox-2- and NCAM-positive neural plate, which was concomitant with the outer shift of ADAM13-positive region. The Xerl injection resulted in incomplete neural closure because of the local overproduction of the neuroepithelium. In contrast, loss of function analysis of Xerl indicated that Xerl inhibition caused the ectopic differentiation of neural crest cells. In the conjugation experiment using chordin-injected animal caps, Xerl promoted chordin-induced XlSox-2 expression, whereas Xerl inhibition caused ADAM13expression even in the injection with a high dose of chordin. Animal cap assays also showed that Xerl expression was induced by chordin. In the functional analysis using truncated forms of Xerl, Xerl deltaL (lacking LNS domain) worked as a dominant negative form that induced the overproduction of neural crest cells. These results suggest that Xerl is involved in the boundary formation of the neural plate through exclusion of neural crest cell differentiation.