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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
2006 (English)In: European journal of histochemistry, ISSN 1121-760X, Vol. 50, no 2, 147-154 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2006. Vol. 50, no 2, 147-154 p.
Keyword [en]
Chicken, Migration, Neurogenesis, Retinogenesis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-94830DOI: 10.4081/987ISI: 000203125500009PubMedID: 16864127OAI: oai:DiVA.org:uu-94830DiVA: diva2:168822
Available from: 2006-09-28 Created: 2006-09-28 Last updated: 2012-03-09Bibliographically approved
In thesis
1. Neuronal Development in the Embryonic Retina: Focus on the Characterization, Generation and Development of Horizontal Cell Subtypes
Open this publication in new window or tab >>Neuronal Development in the Embryonic Retina: Focus on the Characterization, Generation and Development of Horizontal Cell Subtypes
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 170
Keyword
Neurosciences, Activin, Chick, Follistatin, Interneuron, Isl1, Lim1, Migration, Neurogenesis, Prox1, Transcription factor, Neurovetenskap
Identifiers
urn:nbn:se:uu:diva-7128 (URN)91-554-6645-1 (ISBN)
Public defence
2006-10-20, B41, Biomedicinskt centrum (BMC), Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-09-28 Created: 2006-09-28Bibliographically approved

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