Delta-mediated specification of midline cell fates in zebrafish embryos

Background: Fate mapping studies have shown that progenitor cells of three vertebrate embryonic midline structures - the floorplate in the ventral neu ral tube, the notochord and the dorsal endoderm - occupy a common region pr ior to gastrulation. This common region of origin raises the possibility th at interactions between midline progenitor cells are important for their sp ecification prior to germ layer formation. Results: One of four known zebrafish homologues of the Drosophila melanogas ter cell-cell signaling gene Delta, deltaA (dlA), is expressed in the devel oping midline, where progenitor cells of the ectodermal floorplate, mesoder mal notochord and dorsal endoderm lie close together before they occupy dif ferent germ layers. We used a reverse genetic strategy to isolate a missens e mutation of dlA, dlA(dx2), which coordinately disrupts the development of floorplate, notochord and dorsal endoderm. The dlA(dx2) mutant embryos had reduced numbers of floorplate and hypochord cells; these cells lie above a nd beneath the notochord, respectively. In addition, mutant embryos had exc ess notochord cells. Expression of a dominant-negative form of Delta protei n driven by mRNA microinjection produced a similar effect. In contrast, ove rexpression of dlA had the opposite effect: fewer trunk notochord cells and excess floorplate and hypochord cells. Conclusion: Our results indicate that Delta signaling is important for the specification of midline cells. The results are most consistent with the hy pothesis that developmentally equivalent midline progenitor cells require D elta-mediated signaling prior to germ layer formation in order to be specif ied as floorplate, notochord or hypochord. (C) Elsevier Science Ltd ISSN 09 60-9822.