Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Cell Cycle
Cell Cycle Proteins
/ genetics
Cell Differentiation
Cell Self Renewal
Gene Expression Regulation, Developmental
Hair Cells, Auditory
Mice
Organ of Corti
/ cytology
Protein Binding
SOXB1 Transcription Factors
/ genetics
Stem Cells
/ cytology
Transcription Factors
/ genetics
YAP-Signaling Proteins
Hippo signaling pathway
Taz
Yap
inner ear
organ of Corti
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
16 06 2020
16 06 2020
Historique:
pubmed:
3
6
2020
medline:
15
9
2020
entrez:
3
6
2020
Statut:
ppublish
Résumé
Precise control of organ growth and patterning is executed through a balanced regulation of progenitor self-renewal and differentiation. In the auditory sensory epithelium-the organ of Corti-progenitor cells exit the cell cycle in a coordinated wave between E12.5 and E14.5 before the initiation of sensory receptor cell differentiation, making it a unique system for studying the molecular mechanisms controlling the switch between proliferation and differentiation. Here we identify the Yap/Tead complex as a key regulator of the self-renewal gene network in organ of Corti progenitor cells. We show that Tead transcription factors bind directly to the putative regulatory elements of many stemness- and cell cycle-related genes. We also show that the Tead coactivator protein, Yap, is degraded specifically in the Sox2-positive domain of the cochlear duct, resulting in down-regulation of Tead gene targets. Further, conditional loss of the
Identifiants
pubmed: 32482884
pii: 2000175117
doi: 10.1073/pnas.2000175117
pmc: PMC7306825
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Cell Cycle Proteins
0
SOXB1 Transcription Factors
0
Sox2 protein, mouse
0
Transcription Factors
0
YAP-Signaling Proteins
0
Yap1 protein, mouse
0
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
Pagination
13552-13561Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL118761
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC006283
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127717
Pays : United States
Organisme : NIDCD NIH HHS
ID : F31 DC017376
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC014832
Pays : United States
Organisme : NIDCD NIH HHS
ID : T32 DC009975
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130804
Pays : United States
Organisme : NIDCD NIH HHS
ID : R21 DC016984
Pays : United States
Organisme : NIDCD NIH HHS
ID : R01 DC015829
Pays : United States
Organisme : NIDCD NIH HHS
ID : T32 DC000022
Pays : United States
Déclaration de conflit d'intérêts
J.F.M. is a founder and owns shares in Yap therapeutics.
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