CD44 is a marker for the outer pillar cells in the early postnatal mouse inner ear.
Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 ( P244R/ ) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells.
Hertzano
Ronna
R
Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, 16 South Eutaw Street, Baltimore, MD 21201, USA. rhertzano@smail.umaryland.edu
Puligilla
Chandrakala
C
Chan
Siaw-Lin
SL
Timothy
Caroline
C
Depireux
Didier A
DA
Ahmed
Zubair
Z
Wolf
Jeffrey
J
Eisenman
David J
DJ
Friedman
Thomas B
TB
Riazuddin
Sheikh
S
Kelley
Matthew W
MW
Strome
Scott E
SE
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D003638:Deafness / Q000235:genetics; D007758:Ear, Inner / Q000254:growth & development; D020869:Gene Expression Profiling; D006309:Hearing / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007760:Labyrinth Supporting Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; D018960:Hyaluronan Receptors; D020033:Protein Isoforms; C496366:Fgfr3 protein, mouse; D051498:Receptor, Fibroblast Growth Factor, Type 3
Dev Dyn. 2007 Jul;236(7):1905-17
17557302
Am J Med Genet A. 2005 Nov 1;138(4):392-5
16158433
J Cell Biol. 1997 Jun 16;137(6):1287-307
9182663
J Immunol. 1999 Nov 1;163(9):4917-23
10528194
Immunol Today. 2000 Aug;21(8):383-90
10916141
Inflamm Allergy Drug Targets. 2009 Jul;8(3):208-20
19601881
Annu Rev Genet. 2009;43:411-37
19694516
Cell Mol Immunol. 2006 Oct;3(5):359-65
17092433
Semin Cancer Biol. 2008 Aug;18(4):251-9
18450475
J Neurosci. 2001 Jan 15;21(2):570-80
11160436
Curr Protoc Immunol. 2008 Feb;Appendix 4:4A
18432634
Nat Neurosci. 2006 Mar;9(3):443-52
16491081
J Neurosci Methods. 2008 Sep 15;174(1):10-7
18640154
Brain Res Bull. 2003 Jun 15;60(5-6):397-422
12787864
Int J Dev Biol. 2007;51(6-7):571-83
17891718
Development. 1998 Oct;125(20):3935-46
9735355
Brain Res. 2006 May 26;1091(1):282-8
16616734
J Neurosci. 2002 Nov 1;22(21):9368-77
12417662
Hum Mol Genet. 2009 Jan 1;18(1):43-50
18818193
Biochim Biophys Acta. 2009 Feb;1792(2):140-7
19073250
Hum Mol Genet. 2004 Sep 15;13(18):2143-53
15254021
Dev Cell. 2009 Jan;16(1):58-69
19154718
J Neurosci. 2000 Dec 15;20(24):RC116
11125015
Immunology. 1988 May;64(1):37-43
2454887
Immunogenetics. 1989;29(6):402-4
2659502
Cell. 1990 Jun 29;61(7):1303-13
1694723
Am J Hum Genet. 2001 Jul;69(1):25-34
11398101
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18396-401
19011097
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9815-9
7568224
Dev Dyn. 1997 Jan;208(1):1-10
8989516
Br Med Bull. 2002;63:5-24
12324381
Mol Pathol. 1999 Aug;52(4):189-96
10694938
Dev Dyn. 2007 Feb;236(2):525-33
17117437
Mech Dev. 1999 Jun;84(1-2):169-72
10473135
Nat Genet. 1996 Apr;12(4):390-7
8630492
Dev Dyn. 2004 Apr;229(4):802-12
15042704
Dev Biol. 1993 Feb;155(2):423-30
8432397
Dev Neurobiol. 2008 Mar;68(4):434-45
18172891
Nature. 2006 Jun 22;441(7096):984-7
16791196
Blood. 1997 Sep 15;90(6):2217-33
9310473
Gene Expr Patterns. 2007 Aug;7(7):798-807
17604700