title: A central to peripheral progression of cell cycle exit and hair cell differentiation in the developing mouse cristae.
abstract: The inner ear contains six distinct sensory organs that each maintains some ability to regenerate hair cells into adulthood. In the postnatal cochlea, there appears to be a relationship between the developmental maturity of a region and its ability to regenerate as postnatal regeneration largely occurs in the apical turn, which is the last region to differentiate and mature during development. In the mature cristae there are also regional differences in regenerative ability, which led us to hypothesize that there may be a general relationship between the relative maturity of a region and the regenerative competence of that region in all of the inner ear sensory organs. By analyzing adult mouse cristae labeled embryonically with BrdU, we found that hair cell birth starts in the central region and progresses to the periphery with age. Since the peripheral region of the adult cristae also maintains active Notch signaling and some regenerative competence, these results are consistent with the hypothesis that the last regions to develop retain some of their regenerative ability into adulthood. Further, by analyzing embryonic day 14.5 inner ears we provide evidence for a wave of hair cell birth along the longitudinal axis of the cristae from the central regions to the outer edges. Together with the data from the adult inner ears labeled with BrdU as embryos, these results suggest that hair cell differentiation closely follows cell cycle exit in the cristae, unlike in the cochlea where they are uncoupled.
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, United States; Graduate Program in Neuroscience, University of Washington, Seattle, WA 98195, United States.
authors.forename: Amber D
authors.initials: AD
authors.lastname: Slowik
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, WA 98195, United States; Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98109, United States. Electronic address: oliviab@uw.edu.
authors.forename: Olivia
authors.initials: O
authors.lastname: Bermingham-McDonogh
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation; D003051:Cochlea / Q000196:embryology*; D005260:Female; D054777:Hair Cells, Ampulla / Q000166:cytology*; D006198:Hair Cells, Auditory / Q000166:cytology*; D006309:Hearing / Q000502:physiology; D051379:Mice; D038081:Organogenesis / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction; D062206:Spatial Analysis
chemical_list: D051880:Receptors, Notch; D001973:Bromodeoxyuridine
references.citation: Cell Tissue Res. 2010 May;340(2):303-21
references.pmid: 20424840
references.citation: Development. 2015 May 1;142(9):1561-71
references.pmid: 25922522
references.citation: Science. 1993 Mar 12;259(5101):1619-22
references.pmid: 8456285
references.citation: Science. 1993 Mar 12;259(5101):1616-9
references.pmid: 8456284
references.citation: J Assoc Res Otolaryngol. 2000 Sep;1(2):161-71
references.pmid: 11545143
references.citation: J Comp Neurol. 2003 Aug 18;463(2):177-95
references.pmid: 12815755
references.citation: Int J Biochem Cell Biol. 2014 Jan;46:80-9
references.pmid: 24239741
references.citation: Cold Spring Harb Perspect Biol. 2012 Aug;4(8):a008409
references.pmid: 22855724
references.citation: Dev Biol. 2008 Apr 1;316(1):87-99
references.pmid: 18291358
references.citation: Ann N Y Acad Sci. 1996 Jun 19;781:666-9
references.pmid: 8694471
references.citation: Ann Otol Rhinol Laryngol. 1976 Sep-Oct;85(5 suppl 32 pt.4):1-19
references.pmid: 136222
references.citation: Nat Rev Mol Cell Biol. 2005 Oct;6(10):777-88
references.pmid: 16314867
references.citation: Ann Otol Rhinol Laryngol. 1976 Mar-Apr;85(2 pt.1):225-33
references.pmid: 944548
references.citation: Cell Cycle. 2006 Oct;5(20):2314-8
references.pmid: 17102618
references.citation: Acta Otolaryngol Suppl. 1985;422:1-69
references.pmid: 3877398
references.citation: J Neurosci. 2012 May 9;32(19):6600-10
references.pmid: 22573682
references.citation: PLoS One. 2014;9(2):e89377
references.pmid: 24586731
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):13851-6
references.pmid: 23918377
references.citation: Naturwissenschaften. 2000 Feb;87(2):83-6
references.pmid: 10663140
references.citation: J Neurosci. 2011 Oct 26;31(43):15329-39
references.pmid: 22031879
references.citation: Development. 2012 Jan;139(2):245-57
references.pmid: 22186725
references.citation: Acta Otolaryngol Suppl. 1995;520 Pt 1:174-7
references.pmid: 8749111
references.citation: Nat Commun. 2015;6:6613
references.pmid: 25849379
references.citation: Nat Neurosci. 2000 Jun;3(6):580-6
references.pmid: 10816314
references.citation: Hear Res. 2003 Jun;180(1-2):114-25
references.pmid: 12782359
references.citation: Development. 2005 Oct;132(19):4353-62
references.pmid: 16141228
references.citation: J Mol Med (Berl). 2006 Jan;84(1):37-45
references.pmid: 16283144
references.citation: Stem Cell Reports. 2014 Mar 11;2(3):311-22
references.pmid: 24672754
references.citation: Development. 2014 Feb;141(4):816-29
references.pmid: 24496619
references.citation: Neuroreport. 2007 Dec 3;18(18):1911-4
references.pmid: 18007185
references.citation: J Neurosci. 2012 Oct 24;32(43):15093-105
references.pmid: 23100430
references.citation: J Neurosci. 2012 May 9;32(19):6570-7
references.pmid: 22573679
references.citation: J Neurosci. 2001 Jul 1;21(13):4712-20
references.pmid: 11425898
references.citation: Front Cell Neurosci. 2015 Mar 31;9:110
references.pmid: 25873862
references.citation: Nature. 2006 Jun 22;441(7096):984-7
references.pmid: 16791196
references.citation: Dev Cell. 2009 Jan;16(1):58-69
references.pmid: 19154718
references.citation: Development. 2006 Aug;133(15):2817-26
references.pmid: 16790479
references.citation: J Neurosci. 1997 Nov 1;17(21):8270-82
references.pmid: 9334402
references.citation: Dev Biol. 2007 Jul 1;307(1):165-78
references.pmid: 17531970
references.citation: Audiol Neurootol. 2003 Mar-Apr;8(2):80-90
references.pmid: 12634456
references.citation: Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):166-71
references.pmid: 25535395
references.citation: Int J Dev Neurosci. 1997 Jul;15(4-5):433-46
references.pmid: 9263024
references.citation: J Assoc Res Otolaryngol. 2013 Dec;14(6):813-28
references.pmid: 23989618
references.citation: Hear Res. 1999 Jul;133(1-2):53-60
references.pmid: 10416864
references.citation: Development. 2000 Nov;127(21):4551-60
references.pmid: 11023859
references.citation: Hear Res. 2009 Jan;247(1):17-26
references.pmid: 18809482
references.citation: J Comp Neurol. 1998 Jul 20;397(1):69-88
references.pmid: 9671280
references.citation: Otolaryngol Head Neck Surg. 1998 Sep;119(3):255-62
references.pmid: 9743081
references.citation: Hear Res. 1995 Sep;89(1-2):194-202
references.pmid: 8600126
references.citation: J Neurosci. 2014 Nov 19;34(47):15751-63
references.pmid: 25411503
references.citation: Hear Res. 2008 Sep;243(1-2):1-10
references.pmid: 18573326
references.citation: Brain Res. 2006 Jul 7;1098(1):33-48
references.pmid: 16764839
references.citation: J Otolaryngol. 2000 Dec;29(6):351-60
references.pmid: 11770143
references.citation: PLoS One. 2011;6(10):e23729
references.pmid: 22028767
references.citation: Acta Otolaryngol. 1967;:Suppl 220:1-44
references.pmid: 6067797
references.citation: Science. 1995 Feb 3;267(5198):701-7
references.pmid: 7839150
references.citation: J Neurosci. 2011 Aug 17;31(33):11855-66
references.pmid: 21849546
references.citation: Int J Dev Neurosci. 1997 Jul;15(4-5):447-61
references.pmid: 9263025
references.citation: J Assoc Res Otolaryngol. 2009 Sep;10(3):321-40
references.pmid: 19373512
references.citation: J Neurosci. 2012 May 9;32(19):6699-710
references.pmid: 22573692
references.citation: J Neurosci. 2012 Sep 12;32(37):12876-84
references.pmid: 22973011
references.citation: J Comp Neurol. 1982 Mar 20;206(1):1-8
references.pmid: 6124561
references.citation: Nat Neurosci. 2004 Dec;7(12):1310-8
references.pmid: 15543141
references.citation: Curr Biol. 2000 Jun 1;10(11):659-62
references.pmid: 10837254
references.citation: Neuron. 2013 Jan 9;77(1):58-69
references.pmid: 23312516
references.citation: Acta Otolaryngol Suppl. 1971;285:1-77
references.pmid: 4334052
references.citation: Nat Genet. 1999 Mar;21(3):289-92
references.pmid: 10080181
references.citation: J Assoc Res Otolaryngol. 2012 Oct;13(5):609-27
references.pmid: 22752453
references.citation: Mol Ther. 2013 Apr;21(4):834-41
references.pmid: 23439501
references.citation: Development. 2002 May;129(10):2495-505
references.pmid: 11973280