A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea
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...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/47613 |
| _version_ | 1818028475189035008 |
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| author | Meenakshi Prajapati-DiNubila Ana Benito-Gonzalez Erin Jennifer Golden Shuran Zhang Angelika Doetzlhofer |
| author_facet | Meenakshi Prajapati-DiNubila Ana Benito-Gonzalez Erin Jennifer Golden Shuran Zhang Angelika Doetzlhofer |
| author_sort | Meenakshi Prajapati-DiNubila |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:04:23Z |
| format | Article |
| id | doaj.art-bab677c29fa7438d8a32ec56ccfe1007 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:04:23Z |
| publishDate | 2019-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-bab677c29fa7438d8a32ec56ccfe10072022-12-22T02:01:18ZengeLife Sciences Publications LtdeLife2050-084X2019-06-01810.7554/eLife.47613A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochleaMeenakshi Prajapati-DiNubila0https://orcid.org/0000-0002-4600-9778Ana Benito-Gonzalez1Erin Jennifer Golden2Shuran Zhang3Angelika Doetzlhofer4https://orcid.org/0000-0002-7424-2112Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, United StatesThe 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.https://elifesciences.org/articles/47613inner earcochleaactivin signalingfollistatinhair cellauditory cell differentiation |
| spellingShingle | Meenakshi Prajapati-DiNubila Ana Benito-Gonzalez Erin Jennifer Golden Shuran Zhang Angelika Doetzlhofer A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea eLife inner ear cochlea activin signaling follistatin hair cell auditory cell differentiation |
| title | A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea |
| title_full | A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea |
| title_fullStr | A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea |
| title_full_unstemmed | A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea |
| title_short | A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea |
| title_sort | counter gradient of activin a and follistatin instructs the timing of hair cell differentiation in the murine cochlea |
| topic | inner ear cochlea activin signaling follistatin hair cell auditory cell differentiation |
| url | https://elifesciences.org/articles/47613 |
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