A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea

eLife

Shuran Zhang¹  Ana Benito-Gonzalez¹  Erin Jennifer Golden²  Angelika Doetzlhofer²  Meenakshi Prajapati-DiNubila² 

[1] Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United States;Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States;

关键词: inner ear;    cochlea;    activin signaling;    follistatin;    hair cell;    auditory cell differentiation;   

DOI  :  10.7554/eLife.47613

来源: DOAJ

【 摘 要 】

The mammalian auditory sensory epithelium has one of the most stereotyped cellular patterns known in vertebrates. Mechano-sensory hair cells are arranged in precise rows, with one row of inner and three rows of outer hair cells spanning the length of the spiral-shaped sensory epithelium. Aiding such precise cellular patterning, differentiation of the auditory sensory epithelium is precisely timed and follows a steep longitudinal gradient. The molecular signals that promote auditory sensory differentiation and instruct its graded pattern are largely unknown. Here, we identify Activin A and its antagonist follistatin as key regulators of hair cell differentiation and show, using mouse genetic approaches, that a local gradient of Activin A signaling within the auditory sensory epithelium times the longitudinal gradient of hair cell differentiation. Furthermore, we provide evidence that Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, which constitutes a novel mechanism for limiting the number of inner hair cells being produced.

【 授权许可】

Unknown