Early regionalized gene expression patterns within the otocyst appear to co
rrelate with and contribute to development of mature otic structures. In th
e chick, the transcription factor Pax2 becomes restricted to the dorsal and
entire medial side of the otocyst by stage 16/17. The dorsal region of the
otocyst forms the endolymphatic duct and sac (ED/ES), and the cochlear duc
t is derived from the ventromedial region. In the mouse, however, Pax2 expr
ession is reported only in the ventromedial and not the dorsal otocyst. In
Pax2 null mice, the cochlea is missing or truncated, but vestibular structu
res differentiate normally. Here we demonstrate that in the chick, the emer
ging ED/ES express high levels of Pax2 even when the position of the emergi
ng ED is altered with respect to its environment, either by 180 degrees oto
cyst rotations about the anterior/posterior axis or transplantation of the
otocyst into the hindbrain cavity. However, the Pax2 expression pattern is
plastic in the rest of the otic epithelium after 180 degrees rotation of th
e otocyst. Pax2 is upregulated on the medial side (formerly lateral), and d
ownregulated on the lateral side (formerly medial and expressing Pax2) indi
cating that Pax2 expression is influenced by the environment. Although Pax2
is upregulated in the epithelium after 180 degrees rotations in the region
that should form the cochlear duct, cochlear ducts are truncated or absent
, and the ED/ES emerge in a new ventrolateral position. Ablation of the hin
dbrain at the placode or early otic pit stage alters the timing of regional
ized Pax2 expression in the otocyst. The resulting otocysts and ears are ge
nerally smaller, vestibular structures are abnormal, ED/ES are missing but
cochlear ducts are of normal length. The hindbrain and dorsal periotic mese
nchyme provide unique trophic and patterning information to the dorsal otoc
yst. Our results demonstrate that the ED is the earliest structure patterne
d in the inner ear and that the hindbrain is important for its specificatio
n. We also show that, although normal Pax2 expression is required for cochl
ear duct development, it is downstream of ventral otocyst patterning events
.