Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode

Jayasena, Chathurani S.; Ohyama, Takahiro; Segil, Neil; Groves, Andrew K.

doi:10.1242/dev.017905

Cited by 145 publications

(174 citation statements)

References 73 publications

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“…This creates a positive feedback loop that maintains local Notch and Wnt signaling. Well-studied examples include establishing the Drosophila wing margin and size determination of the mouse otic placode (47,48). It is possible the Wntch module can be coopted to function in different biological processes, and similar mechanisms may be adopted in regulating other localized activity zones.…”

Section: Discussionmentioning

confidence: 99%

Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation

Chen

Jiang

et al. 2013

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

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How organs are shaped to specific forms is a fundamental issue in developmental biology. To address this question, we used the repetitive, periodic pattern of feather morphogenesis on chicken skin as a model. Avian feathers within a single tract extend from dome-shaped primordia to thin conical structures with a common axis of orientation. From a systems biology perspective, the process is precise and robust. Using tissue transplantation assays, we demonstrate that a "zone of polarizing activity," localized in the posterior feather bud, is necessary and sufficient to mediate the directional elongation. This region contains a spatially well-defined nuclear β-catenin zone, which is induced by wingless-int (Wnt)7a protein diffusing in from posterior bud epithelium. Misexpressing nuclear β-catenin randomizes feather polarity. This dermal nuclear β-catenin zone, surrounded by Notch1 positive dermal cells, induces Jagged1. Inhibition of Notch signaling disrupts the spatial configuration of the nuclear β-catenin zone and leads to randomized feather polarity. Mathematical modeling predicts that lateral inhibition, mediated by Notch signaling, functions to reduce Wnt7a gradient variations and fluctuations to form the sharp boundary observed for the dermal β-catenin zone. This zone is also enriched for nonmuscle myosin IIB. Suppressing nonmuscle myosin IIB disrupts directional cell rearrangements and abolishes feather bud elongation. These data suggest that a unique molecular module involving chemical-mechanical coupling converts a pliable chemical gradient to a precise domain, ready for subsequent mechanical action, thus defining the position, boundary, and duration of localized morphogenetic activity that molds the shape of growing organs.anterior-posterior axial orientation | boundary formation | denoising | morphogen gradient

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Section: Discussionmentioning

confidence: 99%

Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation

Chen

Jiang

et al. 2013

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

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“…Notch signaling plays multiple roles in inner ear development, including roles in determining the size of the otic placode (20), in development of the neural and sensory components of the inner ear (16)(17)(18)(19), and in differentiation of the hair cells and supporting cells via lateral inhibition (3)(4)(5)(6)(7). In the mouse, lateral inhibition is mediated by the Delta-like1 (DLL1) and Jagged2 ligands (5,6), which are expressed in the hair cells during differentiation.…”

mentioning

confidence: 99%

Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear

Pan

Jin²,

Stanger

et al. 2010

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

126

165

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Sensorineural deafness and balance dysfunction are common impairments in humans frequently caused by defects in the sensory epithelium of the inner ear, composed of hair cells and supporting cells. Lineage studies have shown that hair cells and supporting cells arise from a common progenitor, but how these progenitors are generated remains unknown. Although various molecules have been implicated in the development of the sensory progenitors, none has been shown to be required for the specification of these progenitors in the mammalian inner ear. Here, using both loss-offunction and gain-of-function approaches, we show that Jagged1 (JAG1)-mediated Notch signaling is both required and sufficient for the generation of the sensory progenitors. Specifically, we find that loss of JAG1 signaling leads to smaller sensory progenitor regions without initial effects on proliferation or cell death, indicating that JAG1 is involved in initial specification events. To further test whether Notch signaling is involved in specification of the sensory progenitors, we transiently expressed an activated form of the Notch1 receptor (NICD) using a combined Tet-On/Cre induction system in the mouse. NICD expression resulted in ectopic hair cells and supporting cells in the nonsensory regions of the cochlea and vestibule. These data indicate that Notch specifies sensory progenitors in the inner ear, and that induction of Notch may be important for regenerating or replacing hair cells and supporting cells in the mammalian inner ear.T he mammalian inner ear contains six separate sensory regions required for hearing and balance. Each sensory organ is composed of two basic cell types, sensory hair cells and associated supporting cells. Lineage studies in the chick have shown that both cell types arise from a common sensory progenitor (1, 2) that differentiates into a hair cell or a supporting cell via lateral inhibition mediated by the Notch signaling pathway (3-7). Lineage studies in the chick and fate-mapping studies in the mouse also have demonstrated that hair cells and supporting cells can share a common lineage with neurons of the statoacoustic ganglion (SAG), which derive from the otocyst and innervate the hair cells in the ear (2,8).At present, the factors that specify the sensory progenitors are not known, although various molecules have been implicated. One major candidate is the high-mobility group (HMG) transcription factor SOX2. SOX2 is expressed in the sensory regions, and loss of SOX2 results in inner ears that develop without any hair cells or supporting cells, likely due to loss of the sensory progenitors (9). However, ectopic expression of SOX2 in cochlear explants does not lead to new sensory regions (10), raising the question as to whether SOX2 is sufficient for sensory specification. Other factors shown to be involved in prosensory development in the inner ear include Wnt, Bmp, Fgf, and Notch signaling pathways (11)(12)(13)(14)(15)(16)(17)(18)(19). Which of these signaling pathways is required for sensory progenitor spe...

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“…The classical Notch pathway, a functional evolutionarily conserved signaling system, is important for the diversification of olfactory and auditory systems (Kelley, 2006;Endo et al, 2012). In the early stage of the developing inner ear, the Notch signal promotes the proliferation of sensory epithelial precursors, but at a later stage, it regulates the differentiation of hair cells through lateral inhibition (Kelley, 2006;Jayasena et al, 2008;Kelley et al, 2009). In our study, the depletion of all members of the miR-200 family possibly led to a loss of lfng translation inhibition that might have enhanced the Notch signal transduction pathway (Johnston et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-200 family members are weakly expressed in the neurosensory epithelia of the developing zebrafish (Danio rerio) inner ear

Du¹,

Cao²,

Zhou³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. MicroRNA-200 family members are expressed in the developing mouse inner ear and in zebrafish (Danio rerio) olfactory epithelia, taste buds, and neuromasts, and have also been shown to be associated with differentiation of olfactory and taste buds. However, the role of the miR-200 family in the inner ear of zebrafish had not been studied. We investigated the expression and function of the miR-200 family in the zebrafish inner ear via in situ hybridization and loss-of-function methods. Expression of the miR-200 family was weak and dispersed throughout the developing zebrafish inner ear. After knockdown of miR-200 family members in the developing inner ear, no significant differences in development were observed compared to the controls. Otic vesicles, otoliths, and semicircular canals appeared normal. Compared with less differentiated olfactory filaments in olfactory epithelia, the development of hair cells and statoacoustic ganglion neurons were normal. The kinocilia and stereocilia of hair cells, the innervation of hair cells, and the formation of ribbon synapses were also unaffected. Overall, we conclude that the miR-200 family has a negligible role in the development of zebrafish inner ear; the functions of the miR-200 family may be organ-specific.

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Notch signaling augments the canonical Wnt pathway to specify the size of the otic placode

Cited by 145 publications

References 73 publications

Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation

Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation

Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear

MicroRNA-200 family members are weakly expressed in the neurosensory epithelia of the developing zebrafish (Danio rerio) inner ear

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