Identification ofcis-element regulating expression of the mouseFgf10 gene during inner ear development

Ohuchi, Hideyo; Yasue, Akihiro; Ono, Katsuhiko; Sasaoka, Shunsuke; Tomonari, Sayuri; Takagi, Akira; Itakura, Mitsuo; Moriyama, Keiji; Noji, Sumihare; Nohno, Tsutomu

doi:10.1002/dvdy.20319

Cited by 48 publications

(78 citation statements)

References 65 publications

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“…Fgf10 is very strongly expressed in the developing cochlear ganglion and all of the developing inner ear prosensory patches, eventually resolving in the cochlear duct to the broad inner sulcus (Pirvola et al 2000;Pauley et al 2003) immediately medial to the developing inner hair cell, which expresses Fgf8. Fgf10-null mutants have severely deranged vestibular system morphogenesis and abnormalities of cochlear and vestibular innervation (Pauley et al 2003;Ohuchi et al 2005), but cochlear duct defects have not been reported and are currently being assessed.…”

Section: Discussionmentioning

confidence: 99%

Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates

Mansour

Urness

2013

Genes Dev.

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The stereotyped arrangement of cochlear sensory and supporting cells is critical for auditory function. Our previous studies showed that Muenke syndrome model mice (Fgfr3 P244R/+ ) have hearing loss associated with a supporting cell fate transformation of two Deiters' cells to two pillar cells. We investigated the developmental origins of this transformation and found that two prospective Deiters' cells switch to an outer pillar cell-like fate sequentially between embryonic day 17.5 (E17.5) and postnatal day 3 (P3). Unexpectedly, the Fgfr3 P244R/+ hearing loss and supporting cell fate transformation are not rescued by genetically reducing fibroblast growth factor 8 (FGF8), the FGF receptor 3c (FGFR3c) ligand required for pillar cell differentiation. Rather, reducing FGF10, which normally activates FGFR2b or FGFR1b, is sufficient for rescue of cochlear form and function. Accordingly, we found that the P244R mutation changes the specificity of FGFR3b and FGFR3c such that both acquire responsiveness to FGF10. Moreover, Fgf10 heterozygosity does not block the Fgfr3 P244R/+ supporting cell fate transformation but instead allows a gradual reversion of fate-switched cells toward the normal phenotype between P5 and at least P14. This study indicates that Deiters' and pillar cells can reversibly switch fates in an FGFdependent manner over a prolonged period of time. This property might be exploited for the regulation of sensory cell regeneration from support cells.

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Section: Discussionmentioning

confidence: 99%

Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates

Mansour

Urness

2013

Genes Dev.

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“…(51) Combined with its role in hair follicle stem cells, (20) the early expression and massive reduction of ear development in Gata3 null mice (41) shows that this gene plays an important role in setting up the proliferation capacity of the otocyst through interactions with SMADs (51) and FGFs. (52) Some evidence for PAX signaling affecting SMADS exists for thyroid development, (53) but this has not been demonstrated for the ear. However, an absence of sensory neurons has been claimed for Pax2 null mice, (42) a claim that needs to be reexamined with more sophisticated techniques.…”

Section: Turning Embryonic Ectoderm Cells Into Otic Neurosensory Cellmentioning

confidence: 99%

“…(27,29,30) In addition, FGF's likely signaling through FGFR2B (80) affect morphogenesis and neurosensory formation. (52,63,81,82) How signals generated by these diffusible factors combine with local signals such as EYA1 (48) to maintain and alter bHLH-gene-mediated neuronal progenitor specification and proliferation is unclear. Based on the limited data and expanding general principles validated in other systems, the following tentative conclusions can be drawn: in general, neuronal stem cells express both glial and neuronal markers such as GFAP and Nestin (79) but also the activator and repressor-type bHLH genes.…”

Section: Molecular Basis Of Otic Neuronal Stem Cell Maintenance and Ementioning

confidence: 99%

The molecular basis of neurosensory cell formation in ear development: a blueprint for hair cell and sensory neuron regeneration?

2006

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SummaryThe inner ear of mammals uses neurosensory cells derived from the embryonic ear for mechanoelectric transduction of vestibular and auditory stimuli (the hair cells) and conducts this information to the brain via sensory neurons. As with most other neurons of mammals, lost hair cells and sensory neurons are not spontaneously replaced and result instead in age-dependent progressive hearing loss. We review the molecular basis of neurosensory development in the mouse ear to provide a blueprint for possible enhancement of therapeutically useful transformation of stem cells into lost neurosensory cells. We identify several readily available adult sources of stem cells that express, like the ectoderm-derived ear, genes known to be essential for ear development. Use of these stem cells combined with molecular insights into neurosensory cell specification and proliferation regulation of the ear, might allow for neurosensory regeneration of mammalian ears in the near future.

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Section: Diffusible Factors Involved In Inner Ear Neurogenesismentioning

confidence: 99%

“…Disruption of FgfR1, the other potential receptor for FGF10, causes defects in the organ of Corti associated with the reduced proliferation of the precursor pool that generates the auditory sensory epithelium (Pirvola et al, 2002). Moreover, FGF10 signalling was proposed to be regulated by GATA3, a zinc finger transcription factor (Ohuchi et al, 2005;Lillevali et al, 2006).Finally, mouse FGF15 is the homologue of chicken and human FGF19 (Wright et al, 2004). Mesodermal chicken Fgf19 has been implicated in otic induction (Ladher et al, 2000;Wright et al, 2004) and it is expressed both in the ganglionar neuroblasts delaminating from the otic epithelium and in the CVG ( Figure 1B).…”

mentioning

confidence: 99%

A network of growth and transcription factors controls neuronal differentation and survival in the developing ear

Sánchez-Calderón¹,

Milo²,

León³

et al. 2007

Int. J. Dev. Biol.

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Inner ear neurons develop from the otic placode and connect hair cells with central neurons in auditory brain stem nuclei. Otic neurogenesis is a developmental process which can be separated into different cellular states that are characterized by a distinct combination of molecular markers. Neurogenesis is highly regulated by a network of extrinsic and intrinsic factors, whose participation in auditory neurogenesis is discussed. Trophic factors include the fibroblast growth factor, neurotrophins and insulin-like peptide families. The expression domains of transcription factor families and their roles in the regulation of intracellular signaling pathways associated with neurogenesis are also discussed. Understanding and defining the key factors and gene networks in the development and function of the inner ear represents an important step towards defeating deafness. KEY WORDS: otic neurogenesis, IGF-I, FGF, inner ear, auditory ganglion, cochlear microarray Otic neurogenesisThe inner ear develops from the otic placode, an ectodermal patch located close to the neural tube that invaginates to form a transitory structure, the otic cup. This cup subsequently closes and pinches off from the ectoderm to generate the otic vesicle ( Figure 1). The otic vesicle is an autonomous structure that contains the information required to generate most of the cell types and structures of the adult inner ear (Bissonnette and Fekete, 1996;Bever et al., 2003; reviewed in Varela-Nieto et al., 2004). The mammalian inner ear is composed of six distinct sensory organs: the three cristae of the semicircular canal, the two maculae of the saccule and utricle and the organ of Corti in the cochlea. The cristae and the maculae are vestibular organs, whereas the organ of Corti is the organ of hearing (reviewed in Moller, 2006). The inner ear cochlear ganglion is formed by bipolar neurons that connect the peripheral sensory receptors or hair cells with central neurons in auditory brain stem nuclei. The correct organogenesis of the inner ear involves a dynamic balance of cell proliferation, differentiation, survival and death, processes that are tightly regulated by a network of extrinsic and intrinsic factors (Frago et al., 2000;Varela-Nieto et al., 2003 andLeon et al., 2004).The process of otic neurogenesis can be separated into different cellular states, each characterized by a distinct combination of molecular markers (summarized in Figure 1A). The first Int. J. Dev. Biol. 51: 557-570 (2007) doi: 10.1387/ijdb.072373hs visible output of otic neurogenesis is the delamination of neural cells (otic neuroblasts) from the otic cup (Fig. 1B). These neuroblasts are committed to generate otic neurons and they populate the cochleo-vestibular ganglion (CVG). This ganglion is generated from a region of the otic vesicle epithelium denominated the prospective neural-sensorial domain and that is defined by the domain in which Ngn1 and Deltal1 are co-expressed at early stages (Adam et al., 1998;Abu-Elmagd et al., 2001). It is believed that both n...

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Identification ofcis-element regulating expression of the mouseFgf10 gene during inner ear development

Cited by 48 publications

References 65 publications

Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates

Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates

The molecular basis of neurosensory cell formation in ear development: a blueprint for hair cell and sensory neuron regeneration?

A network of growth and transcription factors controls neuronal differentation and survival in the developing ear

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