Expression of ERK signaling inhibitors Dusp6, Dusp7, and Dusp9 during mouse ear development

Urness, Lisa D.; Li, Chaoying; Wang, Xiaofen; Mansour, Suzanne L.

doi:10.1002/dvdy.21380

Cited by 38 publications

(35 citation statements)

References 90 publications

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“…The temporal separation of these events and the changes in the transcriptional and epigenetic states of inner ear cells that are likely to occur as development proceeds allow similar sets of signals to be interpreted in different ways. The use of intracellular inhibitory feedback, such as the upregulation of Sprouty genes and pathway-specific phosphatases in response to FGF signaling (Mahoney Rogers et al, 2011;Urness et al, 2008), also allows cells to rapidly cease responding to particular signals in preparation for their next developmental choice. Physical growth and morphogenesis also allow the creation of distinct subdivisions within the inner ear that can develop independently from one another or interact only at precise physical positions (Fekete and Wu, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…1). Differentiating otic placode tissue rapidly upregulates negative regulators of the FGF signaling pathway, such as Sprouty (Spry) genes and the dual-specificity ERK phosphatase MKP3 (Dusp6) (Chambers and Mason, 2000;Urness et al, 2008). This rapid attenuation of FGF signaling is required for the subsequent differentiation of otic tissue, as forced activation of FGF signaling in the OEPD blocks the appearance of later otic markers (Freter et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Shaping sound in space: the regulation of inner ear patterning

2012

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There was an error in Development 139, 245-257.On p. 252, in the second paragraph of the section 'Establishing gradients and boundaries in the developing cochlea', it should read 'In adults…from high (basal) to low (apical).'The authors apologise to readers for this mistake. Development 139, 826 (2012) so is not yet available in most cases. This review will summarize recent findings on the identity of these signaling and morphogen molecules and how they are coordinated in space and time to generate the tissue and cellular architecture of the ear. From placode to ear -how graded signals turn ectoderm into the inner earThe entire inner ear and its associated sensory ganglia derive from the otic placode (see Glossary, Box 1). It is one of a series of cranial placodes that collectively give rise to all craniofacial sensory organs, the lens and a subset of cranial ganglia (Baker and Bronner-Fraser, 2001;Schlosser, 2010). The precursors of different placodes are distributed in an anterior-posterior (AP) sequence around the rostral neural plate (see Glossary, Box 1) termed the pre-placodal domain (PPD) (Schlosser, 2006;Streit, 2007). The PPD is induced by signals, such as FGFs, from both the neural plate and the underlying cranial mesoderm, and inhibition of both Wnt and BMP signaling is required to correctly position the PPD at the neural plate border and to prevent it from extending into the embryonic trunk (Kwon et al., 2010;Litsiou et al., 2005).It is now well established that FGF signals are both necessary and sufficient to induce early otic placode markers from competent pre-placodal ectoderm (Fig. 2) (Ohyama et al., 2007;Schimmang, 2007), although both the location of the FGF signals and the specific FGFs responsible for otic induction vary from species to species. The earliest markers of the future inner ear that are induced in response to FGF signaling are members of the paired homeoboxcontaining Pax2/5/8 transcription factor family -Pax8 in anamniotes and Pax2 in amniotes (Groves and Bronner-Fraser, 2000;Heller and Brandli, 1999;Ohyama and Groves, 2004;Pfeffer et al., 1998). Fate-mapping studies in mice and chick have suggested that although the Pax2-expressing domain is likely to contain all the progenitors of the inner ear, it also harbors cells that will give rise to the epibranchial placodes (see Glossary, Box 1) and epidermis (Ohyama and Groves, 2004;Ohyama et al., 2007;Streit, 2001). This Pax2-expressing progenitor domain has been termed the pre-otic field or the otic-epibranchial progenitor domain (OEPD) (Ladher et al., 2000;Freter et al., 2008).The refinement of the OEPD into distinct otic, epibranchial and epidermal territories is regulated by graded Wnt signals emanating from the midline (Fig. 2) (Ohyama et al., 2006). Examination of the cranial region of Wnt reporter mice revealed that OEPD cells closest to the neural plate, which are fated to form the otic placode, receive high levels of Wnt signaling, whereas more lateral OEPD cells, fated to form epidermis and the epibranchial placodes, receiv...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Shaping sound in space: the regulation of inner ear patterning

2012

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“…However, KRAS G12D -mediated ERK1/2 phosphorylation is transient and becomes markedly reduced in the mutant granulosa cells in vivo and in culture. This transient activation of ERK1/2 is mediated, at least in part, by the upregulation of MKP3, a specific ERK1/2 phosphatase (Camps et al, 2000;Keyse, 2000;Li et al, 2007;Urness et al, 2007;Woods and Johnson, 2006). Mkp3 mRNA was rapidly induced in granulosa cells of wild-type mice in response to hCG and was elevated in Kras G12D mutant ovaries (Fig.…”

Section: Research Articlementioning

confidence: 96%

“…7A). This gene encodes MAPK phosphatase 3 (MKP3), which is an ERK1/2-specific protein phosphatase (Camps et al, 2000;Keyse, 2000;Urness et al, 2007;Woods and Johnson, 2006). Expression of Mkp3 was induced in granulosa cells both in vivo (2-4 hours) and in vitro (1-2 hours) by hCG and AREG stimulation, respectively (Fig.…”

Section: Mkp3 Is Upregulated By Krasmentioning

confidence: 99%

Selective expression ofKrasG12Din granulosa cells of the mouse ovary causes defects in follicle development and ovulation

et al. 2008

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Activation of the RAS family of small G-proteins is essential for follicle stimulating hormone-induced signaling events and the regulation of target genes in cultured granulosa cells. To analyze the functions of RAS protein in granulosa cells during ovarian follicular development in vivo, we generated conditional knock-in mouse models in which the granulosa cells express a constitutively active Kras G12D. The Kras G12D mutant mice were subfertile and exhibited signs of premature ovarian failure. The mutant ovaries contained numerous abnormal follicle-like structures that were devoid of mitotic and apoptotic cells and cells expressing granulosa cell-specific marker genes. Follicles that proceeded to the antral stage failed to ovulate and expressed reduced levels of ovulation-related genes. The human chorionic gonadotropin-stimulated phosphorylation of ERK1/2 was markedly reduced in mutant cells. Reduced ERK1/2 phosphorylation was due, in part, to increased expression of MKP3, an ERK1/2-specific phosphatase. By contrast, elevated levels of phospho-AKT were evident in granulosa cells of immature Kras G12D mice, even in the absence of hormone treatments, and were associated with the progressive decline of FOXO1 in the abnormal follicle-like structures. Thus, inappropriate activation of KRAS in granulosa cells blocks the granulosa cell differentiation pathway, leading to the persistence of abnormal non-mitotic, non-apoptotic cells rather than tumorigenic cells. Moreover, those follicles that reach the antral stage exhibit impaired responses to hormones, leading to ovulation failure. Transient but not sustained activation of RAS in granulosa cells is therefore crucial for directing normal follicle development and initiating the ovulation process.

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“…Temporal bones were dissected from postnatal animals, fixed, embedded in paraffin, sectioned parallel to the modiolus at 10 mm, and hybridized as described (Urness et al 2008). Digoxigeninlabeled cRNA probes were prepared from cDNA-containing plasmids or following PCR amplification of 39 untranslated regions (UTRs) from mouse genomic DNA.…”

Section: Cochlear Rna In Situ Hybridizationmentioning

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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Expression of ERK signaling inhibitors Dusp6, Dusp7, and Dusp9 during mouse ear development

Cited by 38 publications

References 90 publications

Shaping sound in space: the regulation of inner ear patterning

Shaping sound in space: the regulation of inner ear patterning

Selective expression ofKrasG12Din granulosa cells of the mouse ovary causes defects in follicle development and ovulation

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

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