The role of bone morphogenetic protein 4 in inner ear development and function

Blauwkamp, Marsha N.; Beyer, Lisa A.; Kabara, Lisa; Takemura, Keiji; Buck, Timothy; King, W. M.; Dolan, David F.; Barald, Kate F.; Raphael, Yehoash; Koenig, Ronald J.

doi:10.1016/j.heares.2006.12.010

Cited by 22 publications

(31 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, our Bmp4 Tm1/+ mice in Black Swiss background do not circle but a small percentage of Bmp4 heterozygous mice in C57BL/6 background do [35].…”

Section: Resultsmentioning

confidence: 81%

Bmp4 Is Essential for the Formation of the Vestibular Apparatus that Detects Angular Head Movements

et al. 2008

View full text Add to dashboard Cite

Angular head movements in vertebrates are detected by the three semicircular canals of the inner ear and their associated sensory tissues, the cristae. Bone morphogenetic protein 4 (Bmp4), a member of the Transforming growth factor family (TGF-β), is conservatively expressed in the developing cristae in several species, including zebrafish, frog, chicken, and mouse. Using mouse models in which Bmp4 is conditionally deleted within the inner ear, as well as chicken models in which Bmp signaling is knocked down specifically in the cristae, we show that Bmp4 is essential for the formation of all three cristae and their associated canals. Our results indicate that Bmp4 does not mediate the formation of sensory hair and supporting cells within the cristae by directly regulating genes required for prosensory development in the inner ear such as Serrate1 (Jagged1 in mouse), Fgf10, and Sox2. Instead, Bmp4 most likely mediates crista formation by regulating Lmo4 and Msx1 in the sensory region and Gata3, p75Ngfr, and Lmo4 in the non-sensory region of the crista, the septum cruciatum. In the canals, Bmp2 and Dlx5 are regulated by Bmp4, either directly or indirectly. Mechanisms involved in the formation of sensory organs of the vertebrate inner ear are thought to be analogous to those regulating sensory bristle formation in Drosophila. Our results suggest that, in comparison to sensory bristles, crista formation within the inner ear requires an additional step of sensory and non-sensory fate specification.

show abstract

“…Notably, our Bmp4 Tm1/+ mice in Black Swiss background do not circle but a small percentage of Bmp4 heterozygous mice in C57BL/6 background do [35].…”

Section: Resultsmentioning

confidence: 81%

Bmp4 Is Essential for the Formation of the Vestibular Apparatus that Detects Angular Head Movements

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Bone Morphogenetic Protein 4 ( BMP4 ) is a member of the TGF-β superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Recent studies have demonstrated that Bmp4 heterozygous null ( Bmp4+/− ) mice are viable and some adults exhibit an inner ear defect 37. Regarding VDR ( Vitamin D receptor ), it seems to be important for a wide range of reasons and it has several important biological roles.…”

Section: Discussionmentioning

confidence: 99%

Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways

Girotto

Pirastu

Sorice

et al. 2011

Journal of Medical Genetics

View full text Add to dashboard Cite

Background Hearing is a complex trait, but until now only a few genes are known to contribute to variability of this process. In order to discover genes and pathways that underlie auditory function, a genome-wide association study was carried out within the International Consortium G-EAR. Methods Meta-analysis of genome-wide association study's data from six isolated populations of European ancestry for an overall number of 3417 individuals. Results Eight suggestive significant loci (p<10 À7) were detected with a series of genes expressed within the inner ear such as: DCLK1, PTPRD, GRM8, CMIP. Additional biological candidates marked by a single nucleotide polymorphism (SNP) with a suggestive association (p<10

show abstract

“…ABR measurements have proven to be a robust method for analyzing the effects of genetic mutations on hearing in mice, both in mutagenesis screens (Kermany et al, 2006) and in the evaluation of candidate genes (Abraira et al, 2007;Blauwkamp et al, 2007;Polley et al, 2006). In these studies, the candidate genes are transcription factors or morphogens with identified roles in nervous system development.…”

Section: Discussionmentioning

confidence: 99%

Auditory brainstem responses are impaired in EphA4 and ephrin-B2 deficient mice

2008

View full text Add to dashboard Cite

The Eph receptor tyrosine kinases and their membrane-anchored ligands, ephrins, are signaling proteins that act as axon guidance molecules during chick auditory brainstem development. We recently showed that Eph proteins also affect patterns of neural activation in the mammalian brainstem. However, functional deficits in the brainstems of mutant mice have not been assessed physiologically. The present study characterizes neural activation in Eph protein deficient mice in the auditory brainstem response (ABR). We recorded the ABR of EphA4 and ephrin-B2 mutant mice, aged postnatal day 18-20, and compared them to wild type controls. The peripheral hearing threshold of EphA4(-/-) mice was 75% higher than that of controls. Waveform amplitudes of peak 1 (P1) were 54% lower in EphA4(-/-) mice than in controls. The peripheral hearing thresholds in ephrin-B2(lacZ/)(+) mice were also elevated, with a mean value 20% higher than that of controls. These ephrin-B2(lacZ/)(+) mice showed a 38% smaller P1 amplitude. Significant differences in latency to waveform peaks were also observed. These elevated thresholds and reduced peak amplitudes provide evidence for hearing deficits in both of these mutant mouse lines, and further emphasize an important role for Eph family proteins in the formation of functional auditory circuitry.

show abstract

The role of bone morphogenetic protein 4 in inner ear development and function

Cited by 22 publications

References 44 publications

Bmp4 Is Essential for the Formation of the Vestibular Apparatus that Detects Angular Head Movements

Bmp4 Is Essential for the Formation of the Vestibular Apparatus that Detects Angular Head Movements

Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways

Auditory brainstem responses are impaired in EphA4 and ephrin-B2 deficient mice

Contact Info

Product

Resources

About