Dkk3‐Cre BAC transgenic mouse line: a tool for highly efficient gene deletion in retinal progenitor cells

Satō, Shigeru; Inoue, Tatsuya; Terada, Koji; Matsuo, Isao; Aizawa, Shinichi; Tano, Yasuo; Fujikado, Takashi; Furukawa, Takahisa

doi:10.1002/dvg.20318

Cited by 88 publications

(110 citation statements)

References 27 publications

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“…Otx2 is a homeodomain transcription factor that is expressed in early and mature photoreceptors and bipolar cells (Fossat et al, 2007;Nishida et al, 2003). Loss of Otx2 from the retina prevents the development of these cell types, the cells adopting amacrine fate instead (Nishida et al, 2003;Sato et al, 2007). These data show that Otx2 is required for both photoreceptor and bipolar cell fate specification.…”

Section: Introductionmentioning

confidence: 94%

Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development

2010

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SUMMARYPhotoreceptors, rods and cones are the most abundant cell type in the mammalian retina. However, the molecules that control their development are not fully understood. In studies of photoreceptor fate determination, we found that Blimp1 (Prdm1) is expressed transiently in developing photoreceptors. We analyzed the function of Blimp1 in the mouse retina using a conditional deletion approach. Developmental analysis of mutants showed that Otx2 + photoreceptor precursors ectopically express the bipolar cell markers Chx10 (Vsx2) and Vsx1, adopting bipolar instead of photoreceptor fate. However, this fate shift did not occur until the time when bipolar cells are normally specified during development. Most of the excess bipolar cells died around the time of bipolar cell maturation. Our results suggest that Blimp1 expression stabilizes immature photoreceptors by preventing bipolar cell induction. We conclude that Blimp1 regulates the decision between photoreceptor and bipolar cell fates in the Otx2 + cell population during retinal development.

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Section: Introductionmentioning

confidence: 94%

Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development

2010

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“…Otx2 appears to act early in the process by which photoreceptors and bipolar cells acquire their unique identities. The deletion of Otx2 from the retina prevents the development of photoreceptors and bipolar cells, whereas its overexpression can promote the formation of both cell types (Nishida et al, 2003;Koike et al, 2007;Sato et al, 2007;Wang et al, 2014). Accordingly, chromatin immunoprecipitation (ChIP) and enhancer characterization experiments show that Otx2 associates with the promoters and enhancers of genes expressed in both photoreceptors and bipolar cells (Kim et al, 2008;Brzezinski et al, 2013;Samuel et al, 2014).…”

Section: Features Of Retinal and Photoreceptor Developmentmentioning

confidence: 99%

Photoreceptor cell fate specification in vertebrates

2015

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Photoreceptors -the light-sensitive cells in the vertebrate retinahave been extremely well-characterized with regards to their biochemistry, cell biology and physiology. They therefore provide an excellent model for exploring the factors and mechanisms that drive neural progenitors into a differentiated cell fate in the nervous system. As a result, great progress in understanding the transcriptional network that controls photoreceptor specification and differentiation has been made over the last 20 years. This progress has also enabled the production of photoreceptors from pluripotent stem cells, thereby aiding the development of regenerative medical approaches to eye disease. In this Review, we outline the signaling and transcription factors that drive vertebrate photoreceptor development and discuss how these function together in gene regulatory networks to control photoreceptor cell fate specification.

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“…Because Oc2 is closely related to Oc1, binds to the same DNA motif, and has a similar expression pattern, it is likely that Oc2 functions similarly in promoting the HC lineage. Interestingly, Otx2, a homeodomain transcription factor involved in photoreceptor fates, is also required for HC formation (31). It remains to be investigated how the onecut factors and Otx2 interact in the regulatory hierarchy of HC genesis.…”

Section: Potential Mechanisms By Which Oc1 and Oc2 Function In Multiplementioning

confidence: 99%

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

Sapkota

Chintala

et al. 2014

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

136

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Previously, we have shown that Onecut1 (Oc1) and Onecut2 (Oc2) are expressed in retinal progenitor cells, developing retinal ganglion cells (RGCs), and horizontal cells (HCs). However, in Oc1-null mice, we only observed an 80% reduction in HCs, but no defects in other cell types. We postulated that the lack of defects in other cell types in Oc1-null retinas was a result of redundancy with Oc2. To test this theory, we have generated Oc2-null mice and now show that their retinas also only have defects in HCs, with a 50% reduction in their numbers. However, when both Oc1 and Oc2 are knocked out, the retinas exhibit more profound defects in the development of all early retinal cell types, including completely failed genesis of HCs, compromised generation of cones, reduced production (by 30%) of RGCs, and absence of starburst amacrine cells. Cone subtype diversification and RGC subtype composition also were affected in the double-null retina. Using RNA-Seq expression profiling, we have identified downstream genes of Oc1 and Oc2, which not only confirms the redundancy between the two factors and renders a molecular explanation for the defects in the double-null retinas, but also shows that the onecut factors suppress the production of the late cell type, rods, indicating that the two factors contribute to the competence of retinal progenitor cells for the early retinal cell fates. Our results provide insight into how onecut factors regulate the creation of cellular diversity in the retina and, by extension, in the central nervous system in general.transcription factors | neural development | retinal development | cell fate determination | gene regulation

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Dkk3‐Cre BAC transgenic mouse line: a tool for highly efficient gene deletion in retinal progenitor cells

Cited by 88 publications

References 27 publications

Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development

Blimp1 controls photoreceptor versus bipolar cell fate choice during retinal development

Photoreceptor cell fate specification in vertebrates

Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development

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