Fgf signaling regulates development and transdifferentiation of hair cells and supporting cells in the basilar papilla

被引:31
作者
Jacques, Bonnie E. [1 ,2 ,3 ]
Dabdoub, Alain [2 ]
Kelley, Matthew W. [1 ]
机构
[1] NIDCD, Lab Cochlear Dev, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA
[2] UCSD Sch Med, Dept Surg, Div Otolaryngol, La Jolla, CA 92093 USA
[3] Univ Maryland, Dept Biol, College Pk, MD 20742 USA
关键词
CHICK INNER-EAR; AUDITORY SENSORY EPITHELIUM; GROWTH-FACTOR RECEPTOR; MAMMALIAN COCHLEA; ACOUSTIC TRAUMA; CELLULAR-DIFFERENTIATION; EXPRESSION PATTERNS; PROSENSORY PATCHES; NONSENSORY REGIONS; NOTCH LIGANDS;
D O I
10.1016/j.heares.2012.04.018
中图分类号
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号
100104 ; 100213 ;
摘要
The avian basilar papilla (BP) is a likely homolog of the auditory sensory epithelium of the mammalian cochlea, the organ of Corti. During mammalian development Fibroblast growth factor receptor-3 (Fgfr3) is known to regulate the differentiation of auditory mechanosensory hair cells (HCs) and supporting cells (SCs), both of which are required for sound detection. Fgfr3 is expressed in developing progenitor cells (PCs) and SCs of both the BP and the organ of Corti; however its role in BP development is unknown. Here we utilized an in vitro whole organ embryonic culture system to examine the role of Fgf signaling in the developing avian cochlea. SU5402 (an antagonist of Fgf signaling) was applied to developing BP cultures at different stages to assay the role of Fgf signaling during HC formation. Similar to the observed effects of inhibition of Fgfr3 in the mammalian cochlea, Fgfr inhibition in the developing BP increased the number of HCs that formed. This increase was not associated with increased proliferation, suggesting that inhibition of the Fgf pathway leads to the direct conversion of PCs or supporting cells into HCs, a process known as transdifferentiation. This also implies that Fgf signaling is required to prevent the conversion of PCs and SCs into HCs. The ability of Fgf signaling to inhibit transdifferentiation suggests that its down-regulation may be essential for the initial steps of HC formation, as well as for the maintenance of SC phenotypes. (C) 2012 Published by Elsevier B.V.
引用
收藏
页码:27 / 39
页数:13
相关论文
共 77 条
[1]  
Adam J, 1998, DEVELOPMENT, V125, P4645
[2]   An RNA Interference-Based Screen of Transcription Factor Genes Identifies Pathways Necessary for Sensory Regeneration in the Avian Inner Ear [J].
Alvarado, David M. ;
Hawkins, R. David ;
Bashiardes, Stavros ;
Veile, Rose A. ;
Ku, Yuan-Chieh ;
Powder, Kara E. ;
Spriggs, Meghan K. ;
Speck, Judith D. ;
Warchol, Mark E. ;
Lovett, Michael .
JOURNAL OF NEUROSCIENCE, 2011, 31 (12) :4535-4543
[3]   APPEARANCE AND DISTRIBUTION OF THE 275 KD HAIR-CELL ANTIGEN DURING DEVELOPMENT OF THE AVIAN INNER-EAR [J].
BARTOLAMI, S ;
GOODYEAR, R ;
RICHARDSON, G .
JOURNAL OF COMPARATIVE NEUROLOGY, 1991, 314 (04) :777-788
[4]   Canonical Notch Signaling Is Not Necessary for Prosensory Induction in the Mouse Cochlea: Insights from a Conditional Mutant of RBPjκ [J].
Basch, Martn L. ;
Ohyama, Takahiro ;
Segil, Neil ;
Groves, Andrew K. .
JOURNAL OF NEUROSCIENCE, 2011, 31 (22) :8046-8058
[5]   Math1:: An essential gene for the generation of inner ear hair cells [J].
Bermingham, NA ;
Hassan, BA ;
Price, SD ;
Vollrath, MA ;
Ben-Arie, N ;
Eatock, RA ;
Bellen, HJ ;
Lysakowski, A ;
Zoghbi, HY .
SCIENCE, 1999, 284 (5421) :1837-1841
[6]   FGFR3 expression during development and regeneration of the chick inner ear sensory epithelia [J].
Bermingham-McDonogh, O ;
Stone, JS ;
Reh, TA ;
Rubel, EW .
DEVELOPMENTAL BIOLOGY, 2001, 238 (02) :247-259
[7]   Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear [J].
Brooker, R ;
Hozumi, K ;
Lewis, J .
DEVELOPMENT, 2006, 133 (07) :1277-1286
[8]   Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis [J].
Chen, L ;
Adar, R ;
Yang, X ;
Monsonego, EO ;
Li, CL ;
Hauschka, PV ;
Yayon, A ;
Deng, CX .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (11) :1517-1525
[9]  
Chen P, 2002, DEVELOPMENT, V129, P2495
[10]   DEVELOPMENT OF HAIR CELLS IN EMBRYONIC CHICKS BASILAR PAPILLA [J].
COHEN, GM ;
FERMIN, CD .
ACTA OTO-LARYNGOLOGICA, 1978, 86 (5-6) :342-358