Document Detail


Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium.
MedLine Citation:
PMID:  17855431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inner ear, which contains sensory organs specialized for hearing and balance, develops from an ectodermal placode that invaginates lateral to hindbrain rhombomeres (r) 5-6 to form the otic vesicle. Under the influence of signals from intra- and extraotic sources, the vesicle is molecularly patterned and undergoes morphogenesis and cell-type differentiation to acquire its distinct functional compartments. We show in mouse that Fgf3, which is expressed in the hindbrain from otic induction through endolymphatic duct outgrowth, and in the prospective neurosensory domain of the otic epithelium as morphogenesis initiates, is required for both auditory and vestibular function. We provide new morphologic data on otic dysmorphogenesis in Fgf3 mutants, which show a range of malformations similar to those of Mafb (Kreisler), Hoxa1 and Gbx2 mutants, the most common phenotype being failure of endolymphatic duct and common crus formation, accompanied by epithelial dilatation and reduced cochlear coiling. The malformations have close parallels with those seen in hearing-impaired patients. The morphologic data, together with an analysis of changes in the molecular patterning of Fgf3 mutant otic vesicles, and comparisons with other mutations affecting otic morphogenesis, allow placement of Fgf3 between hindbrain-expressed Hoxa1 and Mafb, and otic vesicle-expressed Gbx2, in the genetic cascade initiated by WNT signaling that leads to dorsal otic patterning and endolymphatic duct formation. Finally, we show that Fgf3 prevents ventral expansion of r5-6 neurectodermal Wnt3a, serving to focus inductive WNT signals on the dorsal otic vesicle and highlighting a new example of cross-talk between the two signaling systems.
Authors:
Ekaterina P Hatch; C Albert Noyes; Xiaofen Wang; Tracy J Wright; Suzanne L Mansour
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-09-12
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  134     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-01     Completed Date:  2008-02-15     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  3615-25     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Markers / metabolism
Body Patterning*
Ear, Inner* / abnormalities,  cytology,  embryology,  metabolism
Epithelium* / anatomy & histology,  embryology,  metabolism
Fibroblast Growth Factor 3 / genetics,  metabolism*
Gene Expression Regulation
Mice
Mice, Inbred C57BL
Morphogenesis*
Phenotype
Wnt Proteins / genetics,  metabolism
Wnt3 Protein
Wnt3A Protein
Grant Support
ID/Acronym/Agency:
R01 DC004185-06/DC/NIDCD NIH HHS; R01 DC004185-07/DC/NIDCD NIH HHS; R01 DC004185-08/DC/NIDCD NIH HHS; R01 DC005608/DC/NIDCD NIH HHS; R01 DC005608-01/DC/NIDCD NIH HHS; R01 DC005608-02/DC/NIDCD NIH HHS; R01 DC005608-03/DC/NIDCD NIH HHS; R01DC04185/DC/NIDCD NIH HHS; R01DC05608/DC/NIDCD NIH HHS; T32GM07464/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Fgf3 protein, mouse; 0/Fibroblast Growth Factor 3; 0/WNT3A protein, human; 0/Wnt Proteins; 0/Wnt3 Protein; 0/Wnt3A Protein; 0/Wnt3a protein, mouse
Comments/Corrections

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