scholarly journals Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development

Development ◽  
2010 ◽  
Vol 137 (4) ◽  
pp. 619-629 ◽  
Author(s):  
J. A. Brzezinski ◽  
D. A. Lamba ◽  
T. A. Reh
Keyword(s):  
Cell Fate ◽  
Bipolar Cell ◽  
Retinal Development

scholarly journals Functional Roles of Otx2 Transcription Factor in Postnatal Mouse Retinal Development

2007 ◽  
Vol 27 (23) ◽  
pp. 8318-8329 ◽  
Author(s):  
Chieko Koike ◽  
Akihiro Nishida ◽  
Shinji Ueno ◽  
Hiromitsu Saito ◽  
Rikako Sanuki ◽  
...  
Keyword(s):  
Cell Fate ◽  
Bipolar Cell ◽  
Functional Role ◽  
Retinal Development ◽  
Terminal Differentiation ◽  
Cell Development ◽  
Bipolar Cells ◽  
Conditional Knockout ◽  
Retinal Bipolar Cells

ABSTRACT We previously reported that Otx2 is essential for photoreceptor cell fate determination; however, the functional role of Otx2 in postnatal retinal development is still unclear although it has been reported to be expressed in retinal bipolar cells and photoreceptors at postnatal stages. In this study, we first examined the roles of Otx2 in the terminal differentiation of photoreceptors by analyzing Otx2; Crx double-knockout mice. In Otx2 +/−; Crx −/− retinas, photoreceptor degeneration and downregulation of photoreceptor-specific genes were much more prominent than in Crx −/− retinas, suggesting that Otx2 has a role in the terminal differentiation of the photoreceptors. Moreover, bipolar cells decreased in the Otx2 +/−; Crx −/− retina, suggesting that Otx2 is also involved in retinal bipolar-cell development. To further investigate the role of Otx2 in bipolar-cell development, we generated a postnatal bipolar-cell-specific Otx2 conditional-knockout mouse line. Immunohistochemical analysis of this line showed that the expression of protein kinase C, a marker of mature bipolar cells, was significantly downregulated in the retina. Electroretinograms revealed that the electrophysiological function of retinal bipolar cells was impaired as a result of Otx2 ablation. These data suggest that Otx2 plays a functional role in the maturation of retinal photoreceptor and bipolar cells.

scholarly journals Simultaneous deletion of Prdm1 and Vsx2 enhancers in the retina alters photoreceptor and bipolar cell fate specification, yet differs from deleting both genes

Development ◽  
2020 ◽  
Vol 147 (13) ◽  
pp. dev190272 ◽  
Author(s):  
Noah B. Goodson ◽  
Michael A. Kaufman ◽  
Ko U. Park ◽  
Joseph A. Brzezinski
Keyword(s):  
Cell Fate ◽  
Bipolar Cell ◽  
Cell Fate Specification ◽  
Fate Specification

scholarly journals Epigenetic regulation of retinal development

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Reza Raeisossadati ◽  
Merari F. R. Ferrari ◽  
Alexandre Hiroaki Kihara ◽  
Issam AlDiri ◽  
Jeffrey M. Gross
Keyword(s):  
Cell Fate ◽  
Epigenetic Regulation ◽  
Developmental Disorders ◽  
Retinal Development ◽  
Treatment Strategies ◽  
Temporal Precision ◽  
Numerous Cell ◽  
Spatio Temporal ◽  
Novel Treatment Strategies ◽  
Retinal Pathologies

AbstractIn the developing vertebrate retina, retinal progenitor cells (RPCs) proliferate and give rise to terminally differentiated neurons with exquisite spatio-temporal precision. Lineage commitment, fate determination and terminal differentiation are controlled by intricate crosstalk between the genome and epigenome. Indeed, epigenetic regulation plays pivotal roles in numerous cell fate specification and differentiation events in the retina. Moreover, aberrant chromatin structure can contribute to developmental disorders and retinal pathologies. In this review, we highlight recent advances in our understanding of epigenetic regulation in the retina. We also provide insight into several aspects of epigenetic-related regulation that should be investigated in future studies of retinal development and disease. Importantly, focusing on these mechanisms could contribute to the development of novel treatment strategies targeting a variety of retinal disorders.

scholarly journals Essential functions of MLL1 and MLL2 in retinal development and cone cell maintenance

2021 ◽  
Author(s):  
Chi Sun ◽  
Xiaodong Zhang ◽  
Philip Andrew Ruzycki ◽  
Shiming Chen
Keyword(s):  
Cell Fate ◽  
Retinal Development ◽  
Horizontal Cell ◽  
Conditional Knockout ◽  
Mouse Retina ◽  
Light Responses ◽  
Photoreceptor Outer Segments ◽  
Similar Phenotype ◽  
Progenitor Cell Proliferation ◽  
Cell Maintenance

MLL1 (KMT2A) and MLL2 (KMT2B) are homologous members of the mixed-lineage leukemia (MLL) family of histone methyltransferases involved in epigenomic transcriptional regulation. Their sequence variants have been associated with neurological and psychological disorders, but little is known about their roles and mechanism of action in CNS development. Using mouse retina as a model, we previously reported the roles of MLL1 in retinal neurogenesis and horizontal cell maintenance. Here we determine roles of MLL2 and MLL1/MLL2 together in retinal development using conditional knockout (CKO) mice. Deleting Mll2 from Chx10+ retinal progenitors resulted in a similar phenotype as Mll1 CKO, but removal of both alleles produced much more severe deficits than each single CKO: 1-month double CKO mutants displayed null light responses in electroretinogram; thin retinal layers, including shorter photoreceptor outer segments with impaired phototransduction gene expression; and reduced numbers of M-cones, horizontal and amacrine neurons, followed by fast retinal degeneration. Despite moderately reduced progenitor cell proliferation at P0, the neurogenic capacity was largely maintained in double CKO mutants. However, upregulated apoptosis and reactive gliosis were detected during postnatal retinal development. Finally, the removal of both MLLs in fated rods produced a normal phenotype, but the CKO in M-cones impaired M-cone function and survival, indicating both cell non-autonomous and autonomous mechanisms. Altogether, our results suggest that MLL1/MLL2 play redundant roles in maintaining specific retinal neurons after cell fate specification and are essential for establishing functional neural networks.

scholarly journals Retinal organoids: a window into human retinal development

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev189746
Author(s):  
Michelle O'Hara-Wright ◽  
Anai Gonzalez-Cordero
Keyword(s):  
Cell Fate ◽  
Developmental Trajectories ◽  
Retinal Development ◽  
Retinal Disease ◽  
Cell Types ◽  
Model Organisms ◽  
Retinal Cell ◽  
Human Retina ◽  
Cell Fate Decisions

ABSTRACTRetinal development and maturation are orchestrated by a series of interacting signalling networks that drive the morphogenetic transformation of the anterior developing brain. Studies in model organisms continue to elucidate these complex series of events. However, the human retina shows many differences from that of other organisms and the investigation of human eye development now benefits from stem cell-derived organoids. Retinal differentiation methods have progressed from simple 2D adherent cultures to self-organising micro-physiological systems. As models of development, these have collectively offered new insights into the previously unexplored early development of the human retina and informed our knowledge of the key cell fate decisions that govern the specification of light-sensitive photoreceptors. Although the developmental trajectories of other retinal cell types remain more elusive, the collation of omics datasets, combined with advanced culture methodology, will enable modelling of the intricate process of human retinogenesis and retinal disease in vitro.

scholarly journals Characterization of retinal development in 13-lined ground squirrels

2021 ◽  
Author(s):  
Sangeetha Kandoi ◽  
Cassandra Martinez ◽  
Dana Merriman ◽  
Deepak A Lamba
Keyword(s):  
Cell Fate ◽  
Ganglion Cells ◽  
Retinal Development ◽  
Disease Model ◽  
Amacrine Cells ◽  
Ground Squirrels ◽  
Human Vision ◽  
Retinal Cell ◽  
Specific Marker ◽  
Cell Type

Purpose: The cone-dominant, 13-lined ground squirrel (13-LGS) retina mimics the human foveal region but retinal development in this useful rodent species has not been reported. Here, the embryonic and postnatal development of the 13-LGS retina was studied to further characterize the species as a practical alternative animal model for investigating cone-based vision in health and disease. Methods: The spatiotemporal expression of key progenitor and cell type markers was examined in retinas from defined embryonic and postnatal stages using immunohistochemistry. Changes in the postnatal gene expression were also assessed by qPCR. Results: The 13-LGS neuroblastic layer expressed key progenitor markers (Sox2, Vsx2, Pax6, and Lhx2) at E18. Sequential cell fate determination evidenced by the first appearance of cell type-specific marker labeling was: at E18, ganglion cells (Brn-3A, HuC/D) and microglia (Iba1); at E24-25.5 shortly before birth, photoreceptor progenitor (Otx2, Recoverin), horizontal and amacrine cells (Lhx1, Oc1); and at P15, bipolar cells (Vsx1, CaBP5) and Muller glia cells (GS, Rlbp1). Photoreceptor maturation indicated by opsin+ outer segments and PNA labeling of cone sheaths was completed at the time of eye opening, P21-24. Conclusions: The timeline and order of retinal cell development in the 13-LGS generally matches that recorded from other mammalian models but with a stark variation in the proportion of various cell types due to cone-dense photoreceptors. This provides a baseline for future examinations of developmental, disease model, and stem cell approach studies employing this emerging rodent model of human vision.

Roles of homeobox and bHLH genes in specification of a retinal cell type

Development ◽  
2001 ◽  
Vol 128 (8) ◽  
pp. 1313-1322 ◽  
Author(s):  
J. Hatakeyama ◽  
K. Tomita ◽  
T. Inoue ◽  
R. Kageyama
Keyword(s):  
Cell Fate ◽  
Bipolar Cell ◽  
Homeobox Gene ◽  
Bipolar Cells ◽  
Inner Nuclear Layer ◽  
Muller Glia ◽  
Müller Glia ◽  
Bhlh Genes ◽  
Glial Fate ◽  
Cell Genesis

Previous analysis of mutant mice has revealed that the bHLH genes Mash1 and Math3, and the homeobox gene Chx10 are essential for generation of bipolar cells, the interneurons present in the inner nuclear layer of the retina. Thus, a combination of the bHLH and homeobox genes should be important for bipolar cell genesis, but the exact functions of each gene remain largely unknown. We have found that in Mash1-Math3 double-mutant retina, which exhibits a complete loss of bipolar cells, Chx10 expression did not disappear but remained in Muller glial cells, suggesting that Chx10 expression per se is compatible with gliogenesis. In agreement with this, misexpression of Chx10 alone with retrovirus in the retinal explant cultures induced generation of the inner nuclear layer cells, including Muller glia, but few of them were mature bipolar cells. Misexpression of Mash1 or Math3 alone did not promote bipolar cell genesis either, but inhibited Muller gliogenesis. In contrast, misexpression of Mash1 or Math3 together with Chx10 increased the population of mature bipolar cells and decreased that of Muller glia. Thus, the homeobox gene provides the inner nuclear layer-specific identity while the bHLH genes regulate the neuronal versus glial fate determination, and these two classes of genes together specify the bipolar cell fate. Moreover, Mash1 and Math3 promoted the bipolar cell fate, but not the other inner nuclear layer-specific neuronal subtypes in the presence of Chx10, raising the possibility that the bHLH genes may be involved in neuronal subtype specification, in addition to simply making the neuronal versus glial fate choice.

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