Ptf1a expression is necessary for correct targeting of spiral ganglion neurons within the cochlear nuclei

Two transcription factors, Atoh1 and Ptf1a, are essential for cochlear nuclei development. Atoh1 is needed to develop glutamatergic neurons, while Ptf1a is required to generate glycinergic and GABAergic neurons that migrate into the cochlear nucleus. While central projections of inner ear afferents are normal following loss of Atoh1, we wanted to know whether the loss of Ptf1a affects central projections. We found that in Ptf1a mutants, initially, afferents show a normal projection; however, a transient posterior expansion of projections to the dorsal cochlear nucleus occurs at a later stage. In addition, in older (E18.5) Ptf1a mutant mice, excessive neuronal branches form beyond the normal projection to the anterior and posterior ventral cochlear nuclei. Our results on Ptf1a null mice are comparable to that observed in loss of function Prickel1, Npr2, or Fzd3 mouse mutants. The disorganized tonotopic projections that we report in Ptf1a mutant embryos might be functionally relevant, but testing this hypothesis requires Ptf1a KO mice at postnatal stages that unfortunately cannot be performed due to their early death.