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Temporal and spatial expression of transcription factors FoxN4, Ptf1a, Prox1, Isl1 and Lim1 mRNA in the developing chick retina
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience. (Hallböök)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience. (Hallböök)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience. (Hallböök)
2008 (English)In: Gene Expression Patterns, ISSN 1567-133X, E-ISSN 1872-7298, Vol. 8, no 2, 117-123 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2008. Vol. 8, no 2, 117-123 p.
Keyword [en]
In situ hybridization, Optic vesicle, Retina, Quantitative RT-PCR, RACE
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-87576DOI: 10.1016/j.modgep.2007.09.004ISI: 000252714300009PubMedID: 18006384OAI: oai:DiVA.org:uu-87576DiVA: diva2:132813
Available from: 2009-01-05 Created: 2008-12-30 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Generation of Retinal Neurons: Focus on the Proliferation and Differentiation of the Horizontal Cells and their Subtypes
Open this publication in new window or tab >>Generation of Retinal Neurons: Focus on the Proliferation and Differentiation of the Horizontal Cells and their Subtypes
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

We have used the chicken retina as a model for investigating cell cycle regulation and cell fate commitment during central nervous system development. This thesis focuses on the characterization of and commitment to the horizontal cell fate in the retina. Horizontal cells are interneurons that provide intraretinal signal processing prior to information relay to the brain. We have identified molecular markers that selectively distinguish the three subtypes of horizontal cells, previously described in the chicken retina based on morphology. Subtype specific birth-dating revealed that horizontal cell subtypes are generated consecutively by biased progenitors that are sensitive to the inhibitory effects of follistatin. Follistatin stimulates proliferation in progenitors by repressing the differentiation signal of activin. Initially, injection of follistatin led to a decrease in committed horizontal cells but as the inhibitory effect dissipated it resulted in an increased number of horizontal cells. During development committed horizontal cell progenitors migrate to the vitreal side of the retina where they become arrested in G2-phase for approximately two days. When the arrest is overcome the horizontal cell progenitors undergo ectopic mitosis followed by migration to their designated layer. The G2-phase arrest is not triggered or maintained by any of the classic G2-arrest pathways such as DNA damage or stress. Nevertheless, we show that the cyclin B1-Cdk1 complex has a central role in maintaining this G2-phase arrest. Two transcription factors, FoxN4 and Ptf1a, are required for the generation of horizontal cells. We show that these factors are also sufficient to promote horizontal cell fate. Overexpression of FoxN4 and Ptf1a resulted in an overproduction of horizontal- and amacrine cells at the expense of ganglion- and photoreceptor cells. We identified Atoh7, a transcription factor required for the generation of ganglion cells, as a Ptf1a transcriptional target for downregulation. Our data support a common horizontal/amacrine lineage separated from the ganglion/photoreceptor lineage by the action of Ptf1a. In conclusion, these data describe several novel characteristics of horizontal cells enhancing our understanding of neural development and cell fate commitment.

Place, publisher, year, edition, pages
Uppsala: Acta Universitalis Upsaliensis, 2011. 48 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 672
Keyword
FoxN4, Ptf1a, PH3, G2-phase, Cell cycle arrest, Differentiation, Fate, Commitment, Neurogenesis, Follistatin
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-150886 (URN)978-91-554-8074-5 (ISBN)
Public defence
2011-05-28, B42, BMC, Husargatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2011-05-06 Created: 2011-04-07 Last updated: 2011-07-01Bibliographically approved

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