Meeting Abstract
The mammalian hearing organ is an ordered cellular assembly with orderly innervation: two types of spiral ganglion neurons (SGNs) innervate two types of differentially distributed hair cells (HCs). HCs and SGNs evolved from single neurosensory cells through gene multiplication and diversification. Independent regulation of HCs and neuronal differentiation through expression of basic Helix-loop-Helix transcription factors (bHLH TFs: Atoh1, Neurog1, Neurod1) led to the evolution of vestibular HC assembly and their type of innervation. In mammals, a vestibular organ was transformed into the cochlea with a single row of IHC, three rows of OHCs and peculiar innervation distribution. We will report on Sox2, Foxg1 and Lmx1a mutants that radically alter the OC cell assembly and its innervation and may have driven the evolutionary reorganization. Genetically manipulating the level of bHLH TFs changes HC type and distribution and allows inferences how that transformation might have happened. We will report on how bHLH TFs regulate OHC/IHC and how misexpression (Atoh1-Cre; Atoh1f/kiNeurog1) alters HC fate and supporting cell development. Using mice with altered HC types and distribution, we will demonstrate innervation changes. We will show reorganization of innervation in mouse mutants with selective loss of IHCs. Using these insights, we will speculate on necessary steps to be taken to convert a random mixture of post-mitotic precursors into the orderly OC through spatially and temporally regulated critical bHLH genes.
