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The relation between the role of the organizer at the gastrula stage and the activity of earlier signals in the specification, maintenance, and regionalization of the developing brain anlage is still controversial. Mouse embryos homozygous for null mutation in the cripto gene die at about 9.0 days postcoitum (d.p.c.) and fail to gastrulate and to form the node (the primary organizer). Here, we study the presence and the distribution of anterior neural plate molecular domains in cripto null mutants. We demonstrate that, in cripto−/− embryos, the main prosencephalic and mesencephalic regions are present and that they assume the correct topological organization. The identity of the anterior neural domains is maintained in mutant embryos at 8.5 d.p.c., as well as in mutant explants dissected at 8.5 d.p.c. and cultured in vitro for 24 h. Our data imply the existence of a stable neural regionalization of anterior character inside the cripto−/− embryos, despite the failure in both the gastrulation process and node formation. These results suggest that, in mouse embryos, the specification of the anterior neural identities can be maintained without an absolute requirement for the embryonic mesoderm and the node., This work was supported by grants from the BioGem S.C.A.R.1. Associazione Italiana Ricerca sul Cancro (AIRC) and CNR, PS Murst (to G.P.), and by EU grants QLG2-CT-1999-00793, QLRT-1999-31556, 1999-31625, 2000-02310, and Spanish MCT grant DGI BFI2002-02979, DIGESIC-MEC PM98-0056, FEDER-1FD97-2090, and also from the Generalitat Valenciana CTDIA/2002/91 (to S.M. and D.E.). BioGem s.c a r.l. provides R.I. salary. G.L. has been awarded an EMBO short term fellowship.