Cell lineage analysis reveals three different progenitor pools for neurosensory elements in the otic vesicle

Abstract

In the inner ear, sensory versus neuronal specification is achieved through few well-defined bHLH transcription factors. However, the molecular mechanisms regulating the generation of the appropriate cell type in the correct place and at the correct time are not completely understood yet. Various studies have shown that hair cell- and neuron-specifying genes partially overlap in the otic territory, suggesting that mutual interactions among these bHLH factors could direct the generation of the two cell types from a common neurosensory progenitor. Although there is little evidence for a clonal relationship between macular hair cells and sensory neurons, the existence of a single progenitor able to give both sensory and neuronal cell types remains an open question. Here, we identified a population of common neurosensory progenitors in the zebrafish inner ear and studied the proneural requirement for cell fate decision within this population. Expression analysis reveals that proneural genes for hair cells and neurons overlap within the posteromedial otic epithelium. Combined results from single-cell lineage and functional studies on neurog1 and neuroD1 further demonstrate the following: (1) in the anterior region of the ear, neuronal and sensory lineages have already segregated at the onset of proneural gene expression and are committed to a given fate very early; (2) in contrast, the posteromedial part of the ear harbors a population of common progenitors giving both neurons and hair cells until late stages; and finally (3) neuroD1 is required within this pool of bipotent progenitors to generate the hair cell fate. ; The work was funded by Ministry of Science and Innovation Grant BFU2009-07010 (C.P.). D.S. was a recipient of a postdoctoral Juan de la Cierva contract (Ministry of Science and Innovation) and S.D. of a predoctoral FI fellowship (Agency for Management of University and Research Grants, Government of Catalonia)