Localization of bone morphogenetic protein-4 messenger RNA in developing mouse cochlea

Takemura, Teiji; Sakagami, Masafumi; Takebayashi, Kimiko; Umemoto, Masanori; Nakase, Takanobu; Takaoka, Kunio; Kubo, Takeshi; Kitamura, Yukihiko; Nomura, Shosaku

doi:10.1016/0378-5955(95)00233-2

Cited by 25 publications

(19 citation statements)

References 29 publications

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“…3 D and E), which serves as a marker for melanocytes in the stria vascularis (20), and Bmp4 (Fig. 3 F and G), which serves as a marker for Hensen's/Claudius' cells (19,22). The results of these studies demonstrate that Pds is expressed by a set of cochlear cells that reside in a small, delimited area between Tyrp2-and Bmp4-expressing cells.…”

Section: Resultsmentioning

confidence: 57%

Expression pattern of the mouse ortholog of the Pendred’s syndrome gene ( Pds ) suggests a key role for pendrin in the inner ear

Everett

Morsli

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

282

211

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Pendred's syndrome is an autosomalrecessive disorder characterized by deafness and goiter. After our recent identification of the human gene mutated in Pendred's syndrome (PDS), we sought to investigate in greater detail the expression of the gene and the function of its encoded protein (pendrin). Toward that end, we isolated the corresponding mouse ortholog (Pds) and performed RNA in situ hybridization on mouse inner ears (from 8 days postcoitum to postnatal day 5) to establish the expression pattern of Pds in the developing auditory and vestibular systems. Pds expression was detected throughout the endolymphatic duct and sac, in distinct areas of the utricle and saccule, and in the external sulcus region within the cochlea. This highly discrete expression pattern is unlike that of any other known gene and involves several regions thought to be important for endolymphatic f luid resorption in the inner ear, consistent with the putative functioning of pendrin as an anion transporter. These studies provide key first steps toward defining the precise role of pendrin in inner ear development and elucidating the pathogenic mechanism for the deafness seen in Pendred's syndrome.

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Section: Resultsmentioning

confidence: 57%

Expression pattern of the mouse ortholog of the Pendred’s syndrome gene ( Pds ) suggests a key role for pendrin in the inner ear

Everett

Morsli

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

282

211

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“…The effect of BMP4 on promoting differentiation of sensory epithelium progenitor cells is consistent with its temporal and spatial expression in the inner ear sensory organ development [4,6,7]. BMP4 mRNA is expressed in all sensory organ primordia before the hair cells and supporting cells are developed.…”

Section: Discussionmentioning

confidence: 72%

“…In the normal inner ear, BMP4 mRNA is used as a marker to visualize presumptive sensory epithelium [4-7]. At the crucial time during development, when sensory epithelia become postmitotic, epithelial islet-1 expression overlaps with BMP4-expressing areas (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In birds and mammals, the otic placode invaginates and pinches off to form the pear-shaped otic vesicle, or otocyst. The inner ear's sensory epithelia originate from the ventromedial region of the otocyst, an area that can be defined by the expression of several markers, such as BEN (bursal epithelium and neurons)[1], lunatic fringe and cSerrate-1 [2-4], islet-1 [5] and bone morphogentic proteins (BMPs) [4,6,7]. The distinctive temporal and spatial expression patterns of BMP4 in almost all developing chicken inner ear sensory epithelia has led to the suggestion that this protein may play an important role in the induction of inner ear sensory organs [4,6].…”

Section: Introductionmentioning

confidence: 99%

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BMP4 signaling is involved in the generation of inner ear sensory epithelia

Corrales

Wang

et al. 2005

BMC Dev Biol

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BackgroundThe robust expression of BMP4 in the incipient sensory organs of the inner ear suggests possible roles for this signaling protein during induction and development of auditory and vestibular sensory epithelia. Homozygous BMP4-/- animals die before the inner ear's sensory organs develop, which precludes determining the role of BMP4 in these organs with simple gene knockout experiments.ResultsHere we use a chicken otocyst culture system to perform quantitative studies on the development of inner ear cell types and show that hair cell and supporting cell generation is remarkably reduced when BMP signaling is blocked, either with its antagonist noggin or by using soluble BMP receptors. Conversely, we observed an increase in the number of hair cells when cultured otocysts were treated with exogenous BMP4. BMP4 treatment additionally prompted down-regulation of Pax-2 protein in proliferating sensory epithelial progenitors, leading to reduced progenitor cell proliferation.ConclusionOur results implicate BMP4 in two events during chicken inner ear sensory epithelium formation: first, in inducing the switch from proliferative sensory epithelium progenitors to differentiating epithelial cells and secondly, in promoting the differentiation of hair cells within the developing sensory epithelia.

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“…Retinoids, by interfering with the regulation of several gene products present in the cochlea during development (Richardson et al, 1987;Raphael et al, 1988;van de Water et al, 1992;Gerchman et al, 1995), may be important for the differentiation and development of the otic capsule and the statoacoustic receptors (Miyamoto et al, 1995;Shago et al, 1997). Complex interactions with others genes, such as members of the TGF␤ family (Mahmood et al, 1995), basic fibroblast growth factor (Frenz et al, 1994;Takemura et al, 1996), or N-myc (Romand et al, 1994), may also account for the action of retinoids during inner ear development.…”

Section: Discussionmentioning

confidence: 96%

Spatial distributions of retinoic acid receptor gene transcripts in the prenatal mouse inner ear

1998

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The expression patterns of the three mouse retinoic acid (RA) receptor gene isotypes (RAR␣, RAR␤, and RAR␥) and retinoid X receptor gene isotypes (RXR␣, RXR␤, and RXR␥) have been investigated by in situ hybridization analysis of their RNA transcripts in the inner ear of mouse fetuses at 18.5 days of gestation. Two RARs (RAR␣ and RAR␥) and two RXRs (RXR␣ and RXR␤) presented an almost ubiquitous transcript distribution with overlapping expression in several regions of the cochlea, such as Kölliker's organ, the organ of Corti, the spiral limbus, and nervous structures. The organ of Corti showed an enhanced in situ labeling with RAR␣ and RXR␤. By contrast, RAR␤ and RXR␥ displayed more restricted expression patterns. RXR␥ in particular was strongly expressed in Kölliker's organ and in the spiral ganglion. This expression pattern suggests that RA may be involved in the differentiation of several cochlear cell types. Moreover, the colocalization of several RAR and RXR gene transcripts suggests possible heterodimerization between these receptors in several regions of the cochlea.

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Localization of bone morphogenetic protein-4 messenger RNA in developing mouse cochlea

Cited by 25 publications

References 29 publications

Expression pattern of the mouse ortholog of the Pendred’s syndrome gene ( Pds ) suggests a key role for pendrin in the inner ear

Expression pattern of the mouse ortholog of the Pendred’s syndrome gene ( Pds ) suggests a key role for pendrin in the inner ear

BMP4 signaling is involved in the generation of inner ear sensory epithelia

Spatial distributions of retinoic acid receptor gene transcripts in the prenatal mouse inner ear

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