Notch Signaling Influences Neuroprotective and Proliferative Properties of Mature Müller Glia

Ghai, Kanika; Zelinka, Christopher; Fischer, Andy J.

doi:10.1523/jneurosci.4919-09.2010

Cited by 108 publications

(178 citation statements)

References 59 publications

Supporting

Mentioning

166

Contrasting

Unclassified

Order By: Relevance

“…Notch has been shown to be an important pathway for maintaining cell proliferation and survival (24)(25)(26). Thus, JAG1 might be important for the proliferation and/or survival of the sensory progenitors, which could explain the smaller sensory domains observed by marker analysis.…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that along with altering the fate of these cells, Notch also may increase their proliferation. In other systems, Notch is known to affect proliferation (24)(25)(26), and it might play a similar role in the inner ear via JAG1 signaling. This interpretation is also supported by the loss-offunction results in the Jag1-cko inner ear, showing significantly reduced proliferation in the SOX2-positive region at E11.5 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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.

127

165

View full text Add to dashboard Cite

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...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

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.

127

165

View full text Add to dashboard Cite

show abstract

“…Contudo, a ativação apenas desta via não é suficiente para induzir a entrada de células de Müller novamente no ciclo celular, visto que a via de Notch parece atuar em conjunto com a via de MAPK (Ghai et al 2010). A ativação da via de Notch é importante para a proliferação e desdiferenciação em progenitores, mas depois torna-se limitante para a diferenciação neuronal (Hayes et al, 2007).…”

Section: Potencial Regenerativo Das Células Gliais De Müllerunclassified

“…Em aves, o FGF ativa a via MAPK e esta ativação deve ser sustentada para que ocorra a proliferação de células gliais de Müller (Fischer et al, 2009b). Essa via de FGF/MAPK depende da via Notch (Ghai et al, 2010), que tem função temporal específica. É importante que esta seja ativada para que ocorra a desdiferenciação em células progenitoras e que seja inibida para que ocorra a diferenciação em novos neurônios (Hayes et al, 2007).…”

Section: Excitotoxicidade Provocada Por Nmda Estimulou a Proliferaçãounclassified

See 1 more Smart Citation

A GtPase Rac1 participa da proliferação de células gliais de Müller após lesão excitotóxica.

Silva¹

View full text Add to dashboard Cite

An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

Sherpa

Hui

2021

Anim Models and Exp Med

View full text Add to dashboard Cite

The brain processes visual information when light energy transduces into neural activity in the retina. The close-knit components of the central nervous system (CNS), the brain, and its extension retina are thus the critical players in visual perception, thereby aiding in daily activities. While the brain remains well protected inside the skull, the eyes are quite susceptible to physical injuries and chemical accidents. 1 Furthermore, one's genetic makeup and increasing age also invite multiple numbers of eye diseases such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma, etc All this has contributed to the recent "World Reports on vision (2019)," which shows that a whopping 2.2 billion people globally fell victim to visual impairment in the past year. 2 The discovery of the existence of adult retinal stem/progenitor cells among different vertebrate species 3 and its high reparative activity in the case of lower vertebrates has presented us with a possibility to "self-heal" the retina one day. 4 Consequently, high regeneration competent animals, which include the amphibian newts and Xenopus, teleost zebrafish (Danio rerio), and chick are thus being explored 5 to investigate different genetic and epigenetic features, signaling pathways, and factors 6,7 that regulate stem cell activation, thus gradually filling in the gaps of our knowledge of mammals, which appear to be the least competent among the group. 8 With the hope of updating and giving researchers an idea about how these animal models have significantly shaped our understanding of the retinal regeneration process, in this review,

show abstract

Notch Signaling Influences Neuroprotective and Proliferative Properties of Mature Müller Glia

Cited by 108 publications

References 59 publications

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

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

A GtPase Rac1 participa da proliferação de células gliais de Müller após lesão excitotóxica.

An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

Contact Info

Product

Resources

About