| 1. |
- Boije, Henrik, et al.
(författare)
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Horizontal cell progenitors arrest in G2-phase and undergo terminal mitosis on the vitreal side of the chick retina
- 2009
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Ingår i: Developmental Biology. - : Elsevier. - 0012-1606 .- 1095-564X. ; 330:1, s. 105-113
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Tidskriftsartikel (refereegranskat)abstract
- We have addressed the question when horizontal cells in the chick retina are generated and undergo their terminal mitosis. Horizontal cell progenitors replicate their DNA early and migrate bi-directionally to the horizontal cell layer. It was hypothesized that the cells undergo mitosis directly after replication and migrate as post-mitotic transition cells before differentiating to horizontal cells. However, our results show that cells expressing markers for the axon-bearing and the axon-less subtypes of horizontal cells undergo terminal mitosis while residing on the vitreal side of the retina. By combining horizontal cell transcription factors Lim1, Isl1 and Prox1 labeling with phospho-histone H3, a marker for mitosis, we demonstrate that all or a clear majority of vitreal mitoses are undertaken by the horizontal cell committed progenitors. The pattern of cells that incorporated the thymidine analogue EdU implied that the progenitors replicated their genome while migrating towards the vitreal side. Upon arrival to the vitreal retina they become arrested for about two days prior to mitosis. Hence, cells expressing horizontal cell markers are arrested in G2-phase on the vitreal side of the retina. These results support the existence of committed progenitors that give rise to horizontal cells and that those cells become arrested in G2-phase before undergoing terminal mitosis on the vitreal side of the retina followed by migration to the horizontal cell layer. The results also indicate that the regulation of the transition from G2-phase to mitosis is important for the development of these committed progenitor cells.
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| 2. |
- Boije, Henrik, et al.
(författare)
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Temporal and spatial expression of transcription factors FoxN4, Ptf1a, Prox1, Isl1 and Lim1 mRNA in the developing chick retina
- 2008
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Ingår i: Gene Expression Patterns. - : Elsevier BV. - 1567-133X .- 1872-7298. ; 8:2, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Transcription factors are pivotal in regulating cell fate and development. We analyzed five transcription factors - FoxN4, Ptf1a, Prox1, Isl1 and Lim1 - with putative functions in the formation of early-generated retinal interneurons. A full-length chicken FoxN4 cDNA was characterized and in situ as well as RT-PCR showed that FoxN4 expression commenced already in the stage 12-14 optic vesicles. Ptf1a, Prox1, Isl1 and Lim1 expression appeared later by stage 20-24, concomitant with the first post-mitotic ganglion-, amacrine- and horizontal cells. The FoxN4 and Ptf1a expression was transient with peak levels by stage 32-35. Expression disappeared as the retinal progenitor cells differentiated. Prox1, Isl1 and Lim1 expression remained in several differentiated cells including the horizontal cells. The order of expression supports a scheme where Ptf1a and Prox1 is downstream of FoxN4 and that FoxN4 and Ptf1a have transient roles during fate specification while Prox1, Isl1 and Lim1 have roles that are important for the generation of the neuronal subtypes.
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| 3. |
- Edqvist, Per-Henrik D, et al.
(författare)
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Axon-bearing and axon-less horizontal cell subtypes are generated consecutively during chick retinal development from progenitors that are sensitive to follistatin
- 2008
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 8, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Horizontal cells are retinal interneurons that modulate the output from photoreceptors. A rich literature on the morphological classification and functional properties of HCs in different animals exists, however, the understanding of the events underlying their development is still limited. In most vertebrates including chicken, two main horizontal cell (HC) subtypes are identified based on the presence or absence of an axon.RESULTS:In this work we have molecularly characterized three HC subtypes based on Lim1, Isl1, GABA and TrkA, a classification that is consistent with three chick HC subtypes previously defined by morphology. The axon-bearing and axon-less HC subpopulations molecularly defined by Lim1 and Isl1, are born consecutively on embryonic day (E) 3-4 and E4-5, respectively, and exhibit temporally distinguishable periods of migration. Their relative numbers are not adjusted by apoptosis. A sharp decrease of high endogenous levels of the activin-inhibitor follistatin at E3 coincides with the appearance of the Lim1 positive cells. Extending the follistatin exposure of the HC retinal progenitor cells by injection of follistatin at E3 increased the number of both Lim1- and Isl1 positive HCs when analysed at E9.CONCLUSION:The results imply that the axon-bearing and axon-less HC subgroups are defined early and are generated consecutively from a retinal progenitor cell population that is sensitive to the inhibitory action of follistatin. The results are consistent with a model wherein added follistatin causes HC-generating progenitors to proliferate beyond the normal period of HC generation, thus producing extra HCs of both types that migrate to the HC layer.
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| 4. |
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| 5. |
- Edqvist, Per-Henrik, et al.
(författare)
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Early identification of retinal subtypes in the developing, pre-laminated chick retina using the transcription factors Prox1, Lim1, Ap2α, Pax6, Isl1, Isl2, Lim3 and Chx10
- 2006
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Ingår i: European journal of histochemistry. - 1121-760X .- 2038-8306. ; 50:2, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- In this study, antibodies toward the transcription factors Prox1, Lim1, Ap2a, Pax6, Isl1, Isl2, Lim3 and Chx10 were used to identify and distinguish between developing cell types in the pre-laminated chick retina. The spatio-temporal expression patterns were analysed from embryonic day 3 (E3) to E9, thus covering a time-span from the onset of retinal cell-fate determination to when retinal laminas can be distinguished. Most transcription factors were found at early stages of development, enabling us to trace various precursor cell populations throughout the lamination process. With time, each transcription factor expression became restricted to distinct laminas or sub-laminas of the maturing retina. These early emerging patterns were compared and found to be consistent with those of the hatched chick retina, where the outer nuclear layer label for Lim3, Isl1 and Isl2. In the inner nuclear layer, horizontal cells labeled for Prox1, Lim1, Isl1, Ap2a and Pax6, bipolar cell labeled for Lim3, Isl1 and Chx10 and amacrine cells labeled for Ap2a, Isl1 and Pax6. The ganglion cell layer labeled for Isl1, Pax6 and Isl2. The immunolabeling patterns of Lim3 and Isl2 have not previously been described in detail.
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| 6. |
- Edqvist, Per-Henrik, 1978-
(författare)
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Neuronal Development in the Embryonic Retina : Focus on the Characterization, Generation and Development of Horizontal Cell Subtypes
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Horizontal cells are retinal interneurons that modulate the output from photoreceptors. Two horizontal cell (HC) subtypes are commonly identified in the vertebrate retina: axon-bearing and axon-less HCs. In this work, we have identified Isl1 as a novel HC marker and demonstrated that Lim1 and Isl1 distinguish axon-bearing and axon-less HCs, respectively. In the chick retina, axon-less HCs are furthermore split into two different subtypes based on the expression of GABA and TrkA.We have demonstrated that during early chick retinogenesis, HCs expressing either Lim1 or Isl1 are generated consecutively as two equally large sub-groups at different time points. Moreover, these newborn HCs undertake an unexpected bi-directional migration before settling in their final laminar position. Different HC subtypes complete this migration at different times.We investigated the role of activin signaling during HC subtype generation. Activin or its inhibitor follistatin was administrated during the main phase of HC generation and analyzed when HCs had completed migration. Activin caused a significant decrease in both HC subtypes and decreased the proliferation of retinal precursor cells. Follistatin increased the number of late born (Isl1+) HCs, which migrated to the HC-layer during a prolonged migration period. Both treatments affected retinal histology, but only activin influenced the generation of retinal populations other than HCs. These effects were most likely mediated by altered proliferation in certain retinal precursor cells.The data on HC subtype ratios, birth-dates, migration, apoptosis and extrinsic activin modulation favor a scenario where the mature proportions of HC subtypes are generated sequentially from a specific HC-precursor cell lineage early in development and remain stable thereafter. These proportions are not adjusted by apoptosis, but rather by the combined actions of transcription factors and extrinsic signaling. Our studies on HC subtypes and their development promises to facilitate future studies on HC development, evolution and function.
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