期刊
DEVELOPMENT
卷 140, 期 6, 页码 1196-1206出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.087528
关键词
Stem cells; Regeneration; Development; Inner ear; beta-Catenin; Hair cells; Mouse
资金
- Howard Hughes Medical Institute (HHMI) Medical Research Training Fellowship
- Stanford Medical Scholars program
- Stanford Dean's Fellowship
- Hearing Health Foundation
- EMBO long-term fellowship [ALTF 122-2007]
- Dutch Cancer Society
- National Institutes of Health [NIDCD/NIH P30 DC010363, R01 DC006167, K08 DC011043]
- American Otological Society
- Triological Society
- Percy Memorial Award
- Akiko Yamazaki and Jerry Yang Faculty Scholar Fund
- National Organization for Hearing Research Foundation
- Stanford Initiative to Cure Hearing Loss
Permanent hearing loss is caused by the irreversible damage of cochlear sensory hair cells and nonsensory supporting cells. In the postnatal cochlea, the sensory epithelium is terminally differentiated, whereas tympanic border cells (TBCs) beneath the sensory epithelium are proliferative. The functions of TBCs are poorly characterized. Using an Axin2(lacZ) Wnt reporter mouse, we found transient but robust Wnt signaling and proliferation in TBCs during the first 3 postnatal weeks, when the number of TBCs decreases. In vivo lineage tracing shows that a subset of hair cells and supporting cells is derived postnatally from Axin2-expressing TBCs. In cochlear explants, Wnt agonists stimulated the proliferation of TBCs, whereas Wnt inhibitors suppressed it. In addition, purified Axin2(lacZ) cells were clonogenic and self-renewing in culture in a Wnt-dependent manner, and were able to differentiate into hair cell-like and supporting cell-like cells. Taken together, our data indicate that Axin2-positive TBCs are Wnt responsive and can act as precursors to sensory epithelial cells in the postnatal cochlea.
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