Role of bone morphogenetic proteins on cochlear hair cell formation: analyses of Noggin and Bmp2 mutant mice.
The mammalian organ of Corti of the inner ear is a highly sophisticated sensory end organ responsible for detecting sound. Noggin is a secreted glycoprotein, which antagonizes bone morphogenetic proteins 2 and 4 (Bmp2 and Bmp4). The lack of this antagonist causes increased rows of inner and outer hair cells in the organ of Corti. In mice, Bmp2 is expressed transiently in nascent cochlear hair cells. To investigate whether Noggin normally modulates the levels of Bmp2 for hair cell formation, we deleted Bmp2 in the cochlear hair cells using two cre strains, Foxg1(cre/+) and Gfi1(cre/+). Bmp2 conditional knockout cochleae generated using these two cre strains show normal hair cells. Furthermore, Gfi1(cre/+);Bmp2(lox/-) mice are viable and have largely normal hearing. The combined results of Noggin and Bmp2 mutants suggest that Noggin is likely to regulate other Bmps in the cochlea such as Bmp4.
Hwang
Chan Ho
CH
Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland, USA.
Guo
Dayong
D
Harris
Marie A
MA
Howard
Omar
O
Mishina
Yuji
Y
Gan
Lin
L
Harris
Stephen E
SE
Wu
Doris K
DK
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D016057:Evoked Potentials, Auditory, Brain Stem; D051858:Forkhead Transcription Factors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006309:Hearing; D019426:Integrases; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D009925:Organ of Corti / Q000196:embryology* / Q000378:metabolism; D011304:Presbycusis / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D000099176:Noggin Protein
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D019426:Integrases; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C489565:Foxg1 protein, mouse; C079873:Gfi1 protein, mouse; C045073:Cre recombinase