Little is known about the genetic pathways involved in the early steps of i
nner ear morphogenesis. Hoxa1 is transiently expressed in the developing hi
ndbrain; its targeted inactivation in mice results in severe abnormalities
of the otic capsule and membranous labyrinth(1). Here we show that a single
maternal administration of a low dose of the vitamin A metabolite retinoic
acid is sufficient to compensate the requirement for Hoxa1 function. It re
scues cochlear and vestibular defects in mutant fetuses without affecting t
he development of the wildtype fetuses. These results identify a temporal w
indow of susceptibility to retinoids that is critical for mammalian inner e
ar specification, and provide the first evidence that a subteratogenic dose
of vitamin A derivative can be effective in rescuing a congenital defect i
n the mammalian embryo.