First Author | Prajapati-DiNubila M | Year | 2019 |
Journal | Elife | Volume | 8 |
PubMed ID | 31187730 | Mgi Jnum | J:276801 |
Mgi Id | MGI:6316722 | Doi | 10.7554/eLife.47613 |
Citation | Prajapati-DiNubila M, et al. (2019) A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea. Elife 8:e47613 |
abstractText | 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. |