A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea.
activin signaling
auditory cell differentiation
cochlea
developmental biology
follistatin
hair cell
inner ear
mouse
neuroscience
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
12 06 2019
12 06 2019
Historique:
received:
11
04
2019
accepted:
27
05
2019
entrez:
13
6
2019
pubmed:
13
6
2019
medline:
23
2
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31187730
doi: 10.7554/eLife.47613
pii: 47613
pmc: PMC6561706
doi:
pii:
Substances chimiques
Follistatin
0
activin A
0
Activins
104625-48-1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDCD NIH HHS
ID : DC011571
Pays : United States
Organisme : NIDCD NIH HHS
ID : DC005211
Pays : United States
Organisme : NIDCD NIH HHS
ID : F31 DC012972
Pays : United States
Organisme : NIDCD NIH HHS
ID : DC013477
Pays : United States
Organisme : NIDCD NIH HHS
ID : DC012972
Pays : United States
Organisme : NIDCD NIH HHS
ID : F31 DC016538
Pays : United States
Organisme : David M. Rubenstein
ID : Fund for Hearing Research
Pays : International
Organisme : NIDCD NIH HHS
ID : R01 DC011571
Pays : United States
Organisme : NIDCD NIH HHS
ID : DC016538
Pays : United States
Organisme : NIDCD NIH HHS
ID : F32 DC013477
Pays : United States
Informations de copyright
© 2019, Prajapati-DiNubila et al.
Déclaration de conflit d'intérêts
MP, AB, EG, SZ, AD No competing interests declared
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