ABSTRACT
During cochlear development, hair cells (HCs) and supporting cells differentiate in the prosensory domain to form the organ of Corti, but how one row of inner HCs (IHCs) and three rows of outer HCs (OHCs) are organized is not well understood. Here, we investigated the process of HC induction by monitoring Atoh1 expression in cochlear explants of Atoh1-EGFP knock-in mouse embryos and showed that only the cells that express Atoh1 over a certain threshold are selected for HC fate determination. HC induction initially occurs at the medial edge of the prosensory domain to form IHCs and subsequently at the lateral edge to form OHCs, while Hedgehog signaling maintains a space between IHCs and OHCs, leading to formation of the tunnel of Corti. These results reveal dynamic Atoh1 expression in HC fate control and suggest that multi-directional signals regulate OHC induction, thereby organizing the prototype of the organ of Corti.
Footnotes
Author contributions
Conceptualization: T.T., R.K.; Methodology: T.T., S.S., F.I., T.H.; Software: T.H.; Validation: T.T., T.H.; Formal analysis: T.T., T.H.; Investigation: T.T., S.S., F.I.; Resources: I.I.; Data curation: T.T., T.H.; Writing - original draft: T.T., T.H., I.I.; Writing - review & editing: T.T., S.S., F.I., T.H., I.I., R.K.; Visualization: T.T.; Supervision: R.K.; Project administration: T.T., R.K.; Funding acquisition: T.T., I.I., R.K.
Funding
This work was supported by Core Research for Evolutional Science and Technology (CREST) (JPMJCR12W2, R.K.); Grant-in-Aid for Scientific Research on Innovative Areas (16H06480, R.K.) and Scientific Research (C) (25462635, T.T.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan; The Program for Technological Innovation of Regenerative Medicine (JP18bm0704020, I.I.) from the Japan Agency for Medical Research and Development and the Takeda Medical Research Foundation (T.T.).
