Cross-sectional (A) and lumenal surface (B) illustrations of the cellular anatomy of the organ of Corti. Medial and lateral sides are labeled for orientation. A single row of inner hair cells (red) is located on the medial side of the epithelium, while three rows of outer hair cells (red) are located more laterally. Inner hair cells are separated from one another by border cells and inner phalangeal cells (dark green), while outer hair cells are separated by Deiters cells (light green). The inner and outer hair cell regions are separated by the tunnel of Corti, a fluid filled structure that is bounded by single rows of inner and outer pillar cells (purple). Hensen and Claudius cells (beige, yellow) are located at the lateral edge.

Lineages are indicated with black arrows, inductive interactions are marked with green arrows, and inhibitory interactions are marked in red. Briefly, the Notch signaling pathway, along with Sox2 and Eya1, is believed to direct otocyst cells towards a prosensory fate. Next, an undetermined number of prosensory cells become positive for Atoh1, possibly through activation of Fgfr1. Sox2 and Id1, 2, and 3 act to limit the number of cells that become Atoh1 positive. Cells that have begun to develop as hair cells express Jag2, Dll1, and Dll3, leading to activation of Notch1 and the downstream targets Hes1, Hes5, Hey1, Hey2, and Heyl in neighboring prosensory cells. Notch activation inhibits these cells from developing as hair cells. At the same time, hair cells also generate largely unknown inductive signals that recruit neighboring cells to develop as supporting cells. Pillar cell formation is dependent on an inductive interaction between Fgf8, expressed in inner hair cells, and Fgfr3, expressed in progenitor cells, possibly acting through Hey2. Finally, activation of the Hedgehog pathway, possibly mediated through expression of Shh in neuroblasts, acts to inhibit non-sensory cells from moving into the prosensory lineage.

(A) Cross section through the cochlear duct at Embryonic day 13 (E13). Medial is to the left. The prosensory domain is marked by expression of Jag1 (green) and Sox2 (blue) in partially overlapping domains in the floor of the duct. Neurons within the developing spiral ganglion (SG) are labeled in red. The cartoon to the left indicates that spiral ganglion neurons act as a source of sonic hedgehog (Shh) that may act to inhibit sensory formation in the medial half of the duct. (B) Similar view of the duct at E15. Note that the prosensory domain is now located on the lateral half of the floor of the duct. Atoh1-positive hair cells (red) are present within the Jag1/Sox2-positive prosensory domain. A zoomed-in view of the prosensory domain is illustrated in the cartoon. In addition, the patterns of expression for Bmp4 (blue) and Prox1 (gold) are illustrated. (C) Cross-section at E18. Hair cells now express MyosinVI (red). Surrounding supporting cells are still positive for Jag1 (green). Innervating spiral ganglion neurites are labeled in blue. Cartoon summarizes expression patterns for most of the factors discussed in the text.