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 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 presence leading to a significant increase in the expression of Atoh1, Lgr5, and Pou4f3, genes associated with hair cell differentiation. Conversely, overexpression of follistatin delayed hair cell differentiation, reducing Atoh1 and Pou4f3 mRNA expression while increasing Id3 and Id4 expression. 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.