In vertebrates the antero-posterior organization of the embryonic body
axis is thought to result from the activity of two separate centers,
the head organizer and the trunk organizer, as operationally defined b
y Spemann in the 1920s. Current molecular studies have supported the e
xistence of a trunk organizer activity while the presence of a distinc
t head inducing center has remained elusive. Mainly based on analyses
of headless mutants in mice, it has been proposed that the anterior ax
ial mesoderm plays a determining role in head induction. Recent gain-a
nd loss-of-function studies in various organisms, however, provide com
pelling evidence that a largely ignored region, the anterior primitive
endoderm, specifies rostral identity. In this review we discuss the e
merging concept that the anterior primitive endoderm, rather than the
prechordal plate mesoderm, induces head development in the vertebrate
embryo.