Mouse Cerberus-like (Cer-l) is a neural inducer molecule, capable of inhibiting Nodal and BMP-4 signals in the extracelular space. The cer-l expression domain in the Anterior Visceral Endoderm (AVE) and prechordal plate, tissues involved in head induction and patterning, respectively, suggested a role for this gene in head formation. However, animals homozygous for the cerl null allele failed to show any abnormality, leading us to propose the existence of other factor(s) that might compensate for cer-l loss-of-function. Since goosecoid (gsc) shares some domains of expression with cer-l and was shown to be essential for head morphogenesis, we tested its ability to interact genetically with cer-l. With this aim we generated cer-l;gsc double mutants. These animals were analyzed at birth for skeletal defects and revealed the same phenotype as gsc(-/-)single mutants. We also investigated the proper patterning of structures adjacent to the prechordal plate by performing in situ hybridization of HNF-3beta, Six-3 and BF-1, genes whose expression domains remained unchanged. In conclusion, the analysis carried out indicated that gsc does not compensate for cer-l loss-of-function and that these genes do not interact genetically.