A Counter Gradient of Activin A and Follistatin Instructs the Timing of Hair Cell Differentiation in the Murine Cochlea

In 2019, researchers investigated the role of Activin A and its antagonist, follistatin (FST), in hair cell differentiation in the murine cochlea. They discovered that Activin A and follistatin are key regulators of this process. Activin A was found to promote hair cell differentiation, with its signaling within the auditory sensory epithelium timing the longitudinal gradient of hair cell differentiation. Follistatin, on the other hand, maintained pro-sensory cells in a proliferative and undifferentiated state, and its overexpression delayed hair cell differentiation. However, this delay was almost completely abolished when combined with Activin A treatment. The study also revealed a novel mechanism where Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, limiting the number of inner hair cells produced. The researchers concluded that a counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the cochlea.