Overexpression of Math1 induces robust production of extra hair cells in postnatal rat inner ears.
For mammalian cochlear hair cells, fate determination is normally completed by birth. We report here that overexpression of Math1, a mouse homolog of the Drosophila gene atonal, in postnatal rat cochlear explant cultures resulted in extra hair cells. Surprisingly, we found that the source of the ectopic hair cells was columnar epithelial cells located outside the sensory epithelium in the greater epithelial ridge, which normally give rise to inner sulcus cells. Moreover, Math1 expression also facilitated conversion of postnatal utricular supporting cells into hair cells. Thus Math1 was sufficient for the production of hair cells in the ear, and immature postnatal mammalian inner ears retained the competence to generate new hair cells.
Zheng
J L
JL
Department of Neuroscience, MS #72, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Gao
W Q
WQ
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D007758:Ear, Inner / Q000166:cytology* / Q000196:embryology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D007211:Indoles / Q000493:pharmacokinetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D010957:Plasmids / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012444:Saccule and Utricle / Q000166:cytology / Q000187:drug effects; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D007211:Indoles; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C007293:DAPI