Early divergence of central and peripheral neural retina precursors during vertebrate eye development

Venters, Sara J.; Matsukawa, Takashi; Hyer, Jeanette

doi:10.1002/dvdy.24218

Cited by 8 publications

(10 citation statements)

References 104 publications

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“…Interestingly, astrocytes are known to be a heterogeneous cell population ( Bayraktar et al, 2015 ) and our data indicates that Angpt4 + astrocytes represent a specific subpopulation among the glial cells. Intriguingly, genetic deletion revealed that Angpt4 is especially important in the far peripheral segment that may develop via different pathway than central neural retina ( Venters et al, 2015 ). In addition, clinical wide-field fundus imaging has identified a number of vascular diseases in humans in the peripheral retina that can affect also macula even though primary defect is peripheral ( Bajwa et al, 2015 ; Wessel et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina

Elamaa

Kihlström

Kapiainen

et al. 2018

eLife

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The maintenance of fluid homeostasis is necessary for function of the neural retina; however, little is known about the significance of potential ﬂuid management mechanisms. Here, we investigated angiopoietin-4 (Angpt4, also known as Ang3), a poorly characterized ligand for endothelial receptor tyrosine kinase Tie2, in mouse retina model. By using genetic reporter, fate mapping, and in situ hybridization, we found Angpt4 expression in a specific sub-population of astrocytes at the site where venous morphogenesis occurs and that lower oxygen tension, which distinguishes peripheral and venous locations, enhances Angpt4 expression. Correlating with its spatiotemporal expression, deletion of Angpt4 resulted in defective venous development causing impaired venous drainage and defects in neuronal cells. In vitro characterization of angiopoietin-4 proteins revealed both ligand-specific and redundant functions among the angiopoietins. Our study identifies Angpt4 as the first growth factor for venous-specific development and its importance in venous remodeling, retinal fluid clearance and neuronal function.

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Section: Discussionmentioning

confidence: 99%

Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina

Elamaa

Kihlström

Kapiainen

et al. 2018

eLife

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“…The 48-hpf retina comprises the most diversity of RPCs because 48-hpf RPCs at the central region mostly undergo terminal cell divisions, whereas the ones at the peripheral region are still at the earlier stages of embryonic retinal development (He et al, 2012;Rapaport et al, 2004;Venters et al, 2015). Indeed, we were able to characterize seven distinct clusters from 48 hpf RPCs (Cluster 1 to Cluster 7-48 hpf; Fig.…”

Section: Defining Cellular Heterogeneity Of Embryonic Rpcsmentioning

confidence: 91%

Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina

Tang

Jin

et al. 2020

Development

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The zebrafish retina grows for a lifetime. Whether embryonic and postembryonic retinogenesis conform to the same developmental program is an outstanding question that remains under debate. Using single-cell RNA sequencing of ∼20,000 cells of the developing zebrafish retina at four different stages, we identified seven distinct developmental states. Each state explicitly expresses a gene set. Disruption of individual state-specific marker genes results in various defects ranging from small eyes to the loss of distinct retinal cell types. Using a similar approach, we further characterized the developmental states of postembryonic retinal stem cells (RSCs) and their progeny in the ciliary marginal zone. Expression pattern analysis of state-specific marker genes showed that the developmental states of postembryonic RSCs largely recapitulated those of their embryonic counterparts, except for some differences in rod photoreceptor genesis. Thus, our findings reveal the unifying developmental program used by the embryonic and postembryonic retinogenesis in zebrafish.

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“…Here, we applied BMP-beads at later stages of chick eye development. At the time of BMP5 application (E3.5/E4), the peripheral and the proximal RPE can be distinguished by the distribution of signalling components of the Wnt signalling pathway and MITF protein distribution (see also Venters et al, 2015 ). While Wnt2b transcripts are detected in the peripheral RPE, nuclear β-Catenin is detected in the proximal RPE ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…8 A) ( Jasoni et al, 1999 ; Kubo et al, 2003 ; Kitamoto and Hyer, 2010 ). Thus, it is possible that BMP signalling in the presence of WNT2b might induce an RPE cell fate in the peripheral eye, whereas in the WNT2b-negative proximal RPE a conversion into NR is observed ( Figs 8 and 9 ) ( Venters et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

BMP-induced reprograming of the retina into RPE requires WNT signalling in the developing chick optic cup

Steinfeld¹,

Steinfeld²,

Bausch³

et al. 2017

Biology Open

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In vertebrates, the retinal pigment epithelium (RPE) and photoreceptors of the neural retina (NR) comprise a functional unit required for vision. During vertebrate eye development, a conversion of the RPE into NR can be induced by growth factors in vivo at optic cup stages, but the reverse process, the conversion of NR tissue into RPE, has not been reported. Here, we show that bone morphogenetic protein (BMP) signalling can reprogram the NR into RPE at optic cup stages in chick. Shortly after BMP application, expression of Microphthalmia-associated transcription factor (Mitf) is induced in the NR and selective cell death on the basal side of the NR induces an RPE-like morphology. The newly induced RPE differentiates and expresses Melanosomalmatrix protein 115 (Mmp115) and RPE65. BMP-induced Wnt2b expression is observed in regions of the NR that become pigmented. Loss of function studies show that conversion of the NR into RPE requires both BMP and Wnt signalling. Simultaneous to the appearance of ectopic RPE tissue, BMP application reprogrammed the proximal RPE into multi-layered retinal tissue. The newly induced NR expresses visual segment homeobox-containing gene (Vsx2), and the ganglion and photoreceptor cell markers Brn3α and Visinin are detected. Our results show that high BMP concentrations are required to induce the conversion of NR into RPE, while low BMP concentrations can still induce transdifferentiation of the RPE into NR. This knowledge may contribute to the development of efficient standardized protocols for RPE and NR generation for cell replacement therapies.

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Early divergence of central and peripheral neural retina precursors during vertebrate eye development

Cited by 8 publications

References 104 publications

Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina

Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina

Unifying Developmental Programs for Embryonic and Post-Embryonic Neurogenesis in the Zebrafish Retina

BMP-induced reprograming of the retina into RPE requires WNT signalling in the developing chick optic cup

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