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Background  The homeobox gene  Prox1  is required for lens, retina, pancreas, liver, and lymphatic vasculature development and is expressed in inner ear supporting cells and neurons.    Methodology/Principal Findings  We have investigated the role of  Prox1  in the developing mouse ear taking advantage of available standard and conditional  Prox1  mutant mouse strains using  Tg(Pax2-Cre)  and  Tg(Nes-Cre) . A severe reduction in the size of the canal cristae but not of other vestibular organs or the cochlea was identified in the E18.5  Prox1 Flox/Flox ; Tg(Pax2-Cre)  mutant ear. In these mutant embryos, hair cell differentiated; however, their distribution pattern was slightly disorganized in the cochlea where the growth of type II nerve fibers to outer hair cells along  Prox1  expressing supporting cells was severely disrupted. In the case of  Nestin-Cre , we found that newborn  Prox1 Flox/Flox ; Tg(Nestin-Cre)  exhibit only a disorganized innervation of outer hair cells despite apparently normal cellular differentiation of the organ of Corti, suggesting a cell-autonomous function of  Prox1  in neurons.    Conclusions/Significance  These results identify a dual role of  Prox1  during inner ear development; growth of the canal cristae and fiber guidance of Type II fibers along supporting cells in the cochlea.

Canal Cristae Growth and Fiber Extension to the Outer Hair Cells of the Mouse Ear Require Prox1 Activity