The development of semicircular canals in the inner ear: role of FGFs in sensory cristae.
In the vertebrate inner ear, the ability to detect angular head movements lies in the three semicircular canals and their sensory tissues, the cristae. The molecular mechanisms underlying the formation of the three canals are largely unknown. Malformations of this vestibular apparatus found in zebrafish and mice usually involve both canals and cristae. Although there are examples of mutants with only defective canals, few mutants have normal canals without some prior sensory tissue specification, suggesting that the sensory tissues, cristae, might induce the formation of their non-sensory components, the semicircular canals. We fate-mapped the vertical canal pouch in chicken that gives rise to the anterior and posterior canals, using a fluorescent, lipophilic dye (DiI), and identified a canal genesis zone adjacent to each prospective crista that corresponds to the Bone morphogenetic protein 2 (Bmp2)-positive domain in the canal pouch. Using retroviruses or beads to increase Fibroblast Growth Factors (FGFs) for gain-of-function and beads soaked with the FGF inhibitor SU5402 for loss-of-function experiments, we show that FGFs in the crista promote canal development by upregulating Bmp2. We postulate that FGFs in the cristae induce a canal genesis zone by inducing/upregulating Bmp2 expression. Ectopic FGF treatments convert some of the cells in the canal pouch from the prospective common crus to a canal-like fate. Thus, we provide the first molecular evidence whereby sensory organs direct the development of the associated non-sensory components, the semicircular canals, in vertebrate inner ears.
National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850, USA.
Weise
W
Chang
John V
JV
Brigande
Donna M
DM
Fekete
Doris K
DK
Wu
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002352:Carrier Proteins; D019070:Cell Lineage; D002642:Chick Embryo; D007758:Ear, Inner / Q000196:embryology*; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D029961:Zebrafish Proteins; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D051526:Fibroblast Growth Factor 10; D016222:Fibroblast Growth Factor 2; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D011506:Proteins; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C105686:SU 5402; C525826:bmp7a protein, zebrafish; C489200:fgf3 protein, zebrafish