Notch signaling and Atoh1 expression during hair cell regeneration in the mouse utricle.
The mammalian vestibular epithelium has a limited capacity for spontaneous hair cell regeneration. The mechanism underlying the regeneration is not well understood. Because the Notch signaling pathway mediates the formation of the sensory epithelial mosaic patterning during ear development, it may also play a role in hair cell regeneration in the mature mammalian vestibular epithelium after a lesion. To investigate the process of spontaneous regeneration in the vestibular epithelium vis-à-vis changes in Notch signaling, we induced a unilateral lesion by infusing streptomycin into the mouse posterior semicircular canal, and examined Notch signaling molecules and their mRNA expression levels by immunohistochemistry and quantitative real-time polymerase chain reaction (qRTPCR), respectively. We detected Jagged1 in supporting cells in both normal and lesioned utricles. Atoh1, a marker for early developing hair cells, was absent in the intact mature tissue, but re-appeared after the lesion. Many cells were either positive for both Atoh1 and myosin VIIa, or for one of them. qRTPCR data showed a post trauma decrease of Hes5 and an increase in Atoh1. Atoh1 up-regulation may either be a result of Hes5 down-regulation or mediated by another signaling pathway.
Wang
Guo-Peng
GP
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, MI 48109, USA.
Chatterjee
Ishani
I
Batts
Shelley A
SA
Wong
Hiu Tung
HT
Gong
Tzy-Wen
TW
Gong
Shu-Sheng
SS
Raphael
Yehoash
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018069:Hair Cells, Vestibular / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D023421:Models, Animal; D051881:Receptor, Notch1 / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D012444:Saccule and Utricle / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*; D000072056:Transcription Factor HES-1; D015854:Up-Regulation / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; C500943:Atoh1 protein, mouse; C489734:Hes1 protein, mouse; C489685:Hes5 protein, mouse; C000606274:Jag1 protein, mouse; C497762:Notch1 protein, mouse