Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell Populations that Contribute to Retina Growth and Regeneration

Wei, Jin; Goldman, Daniel

doi:10.1016/j.celrep.2017.04.009

Cited by 50 publications

(84 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notch signalling is known to be active in Müller glia (MG) cells and the transit-amplifying zone of the CMZ in the zebrafish post-embryonic retina (Link and Darland, 2001; Raymond et al, 2006). Its role in MG cells, which are the retinal stem cells responsible for retinal regeneration in zebrafish, has been extensively studied (Wan and Goldman, 2017; Wan et al, 2012). However, the function of Notch signalling in lineage specification in the transit-amplifying zone of the CMZ is still unknown.…”

Section: Resultsmentioning

confidence: 99%

Notch signalling patterns retinal composition by regulatingatoh7during post-embryonic growth

Saturnino

Lust

Wittbrodt

2018

Preprint

View full text Add to dashboard Cite

Patterning of a continuously growing naive field in the context of a life-long growing organ, the teleost eye is of highest functional relevance. Intrinsic and extrinsic signals were proposed to regulate lineage specification in progenitors that exit the stem cell niche in the ciliary marginal zone (CMZ). The proper cell type composition arising from those progenitors is prerequisite for retinal function. Our findings in the teleost medaka (Oryzias latipes) uncover that the Notch–Atoh7 axis continuously patterns the CMZ. The complement of cell-types originating from the two juxtaposed progenitors marked by Notch or Atoh7 activity contains all constituents of a retinal column. Modulation of Notch signalling specifically in Atoh7-expressing cells demonstrates the crucial role of this axis in generating the correct cell type proportions. After transiently blocking Notch signalling, retinal patterning and differentiation is reinitiated de novo. Taken together we show that Notch activity in the CMZ continuously structures the growing retina by juxtaposing Notch and Atoh7 progenitors giving rise to distinct, complementary lineages, revealing a coupling of de novo patterning and cell-type specification in the respective lineages.

show abstract

Section: Resultsmentioning

confidence: 99%

Notch signalling patterns retinal composition by regulatingatoh7during post-embryonic growth

Saturnino

Lust

Wittbrodt

2018

Preprint

View full text Add to dashboard Cite

show abstract

“…In the zebrafish retina, MG respond to injury by re-entering the cell cycle, and these MG-derived progenitors then go on to differentiate and regenerate the retina [24]. Notch signaling is dynamically regulated during this process, characterized by an initial decrease followed by an up-regulation of specific Notch components [66-68]. Unlike in mammals, Hes1 expression is maintained in MG in the mature retina [29], and in the absence of damage, Notch maintains MG in a state of quiescence [69] .…”

Section: Pro-regenerative Speciesmentioning

confidence: 99%

“…Additionally, an analysis of retinal regeneration associated miRNA expression has identified miRNAs that contribute to MG-derived progenitor proliferation, and several of these, including miR-7a, miR-146a, and miR-31 have been shown to regulate Notch in other systems [56]. Although repression of Notch can stimulate a small increase in the expression of de-differentiation markers including Ascl1a, this is not sufficient to produce a strong proliferative response in the retina; additional damage related signals are necessary [66, 69, 68]. The identities of many of these damage induced molecules have been uncovered in recent years [66, 68, 70-72] , but more work is needed in understanding the details of how they interact with the Notch signaling pathway.…”

Section: Pro-regenerative Speciesmentioning

confidence: 99%

“…Notch signaling, in turn, represses both HB-EGF and Ascl1a, thereby limiting proliferative capacity to MG-derived progenitors experiencing the greatest concentration of damage induced signals. It has recently been demonstrated that the initial decrease in Notch signaling following injury is dependent on Fgf8a, which itself undergoes an age-dependent switch from the facilitation to the inhibition of proliferation by progenitor cells [68]. Since Fgf8 is not expressed in the mature mammalian retina, this interaction between Notch and Fgf8 may be related to the unique feature of zebrafish retinal regeneration in which Notch is inhibitory, rather than stimulatory.…”

Section: Pro-regenerative Speciesmentioning

confidence: 99%

“…It is important to note that most studies use Notch components such as receptor or Hes gene expression as read-outs, but this approach does not convey the full breadth of Notch related changes, and could potentially be misleading. An accurate depiction requires the use of a Notch signaling reporter, which at this point has only been used in zebrafish [68]. Therefore, a comprehensive understanding of Notch signaling in the MG of non-regenerative species is still lacking, and is likely to be more complex than is currently appreciated.…”

Section: Non-regenerative Speciesmentioning

confidence: 99%

See 2 more Smart Citations

The Regulation of Notch Signaling in Retinal Development and Regeneration

Mills

Goldman

2017

Curr Pathobiol Rep

Self Cite

View full text Add to dashboard Cite

Purpose of review Notch signaling is an important component of retinal progenitor cell maintenance and MG specification during development, and its manipulation may be critical for allowing MG to re-enter the cell cycle and regenerate neurons in adults. In mammals, MG respond to retinal injury by undergoing a gliotic response rather than a regenerative one. Understanding the complexities of Notch signaling may allow for strategies that enhance regeneration over gliosis. Recent findings Notch signaling is regulated at multiple levels, and is interdependent with various other signaling pathways in both the receptor and ligand expressing cells. The precise spatial and temporal patterning of Notch components is necessary for proper retinal development. Regenerative species undergo a dynamic regulation of Notch signaling in MG upon injury, whereas non-regenerative species fail to productively regulate Notch. Summary Notch signaling is malleable, such that the altered composition of growth and transcription factors in the developing and mature retinas result in different Notch mediated responses. Successful regeneration will require the manipulation of the retinal environment to foster a dynamic rather than static regulation of Notch signaling in concert with other reprogramming and differentiation factors.

show abstract

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

Opposing Actions of Fgf8a on Notch Signaling Distinguish Two Muller Glial Cell Populations that Contribute to Retina Growth and Regeneration

Cited by 50 publications

References 44 publications

Notch signalling patterns retinal composition by regulatingatoh7during post-embryonic growth

Notch signalling patterns retinal composition by regulatingatoh7during post-embryonic growth

The Regulation of Notch Signaling in Retinal Development and Regeneration

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

Contact Info

Product

Resources

About