Hans, S., Irmscher, A., and Brand, M. (2013) Zebrafish Foxi1 provides a neuronal ground state during inner ear induction preceding the Dlx3b/4b-regulated sensory lineage. Development (Cambridge, England). 140(9):1936-1945.
Vertebrate inner ear development is a complex process that involves the induction of a common territory for otic and epibranchial
precursors and their subsequent segregation into otic and epibranchial cell fates. In zebrafish, the otic-epibranchial progenitor
domain (OEPD) is induced by Fgf signaling in a Foxi1- and Dlx3b/4b-dependent manner, but the functional differences of Foxi1
and Dlx3b/4b in subsequent cell fate specifications within the developing inner ear are poorly understood. Based on pioneer
tracking (PioTrack), a novel Cre-dependent genetic lineage tracing method, and genetic data, we show that the competence to
embark on a neuronal or sensory fate is provided sequentially and very early during otic placode induction. Loss of Foxi1
prevents neuronal precursor formation without affecting hair cell specification, whereas loss of Dlx3b/4b inhibits hair cell
but not neuronal precursor formation. Consistently, in Dlx3b/4b- and Sox9a-deficient b380 mutants almost all otic epithelial fates are absent, including sensory hair cells, and the remaining otic cells adopt a neuronal
fate. Furthermore, the progenitors of the anterior lateral line ganglia also arise from the OEPD in a Foxi1-dependent manner
but are unaffected in the absence of Dlx3b/4b or in b380 mutants. Thus, in addition to otic fate Foxi1 provides neuronal competence during OEPD induction prior to and independently
of the Dlx3b/4b-mediated sensory fate of the developing inner ear.