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Mechanisms controlling Pax6 isoform expression in the retina have been conserved between teleosts and mammals

Mechanisms controlling Pax6 isoform expression in the retina have been conserved between teleosts and mammals
Mechanisms controlling Pax6 isoform expression in the retina have been conserved between teleosts and mammals

The Pax6 gene plays several roles in retinal development, including control of cell proliferation, maintenance of the retinogenic potential of progenitor cells, and cell fate specification. Emerging evidence suggests that these different aspects of Pax6 gene function are mediated by different isoforms of the Pax6 protein; however, relatively little is known about the spatiotemporal expression of Pax6 isoforms in the vertebrate retina. Using bacterial artificial chromosome (BAC) technology, we modified a zebrafish Pax6a BAC such that we could distinguish paired-containing Pax6a transcripts from paired-less Pax6a transcripts. In the zebrafish, the spatial and temporal onset of expression of these transcripts suggests that the paired-less isoform is involved in the cell fate decision leading to the generation of amacrine cells; however, because of limitations associated with transient transgenic analysis, it was not feasible to establish whether this promoter was active in all amacrine cells or in a specific population of amacrine cells. By making mice transgenic for the zebrafish Pax6a BAC reporter transgene, we were able to show that paired-containing and paired-less Pax6a transcripts were differentially expressed in amacrine subpopulations. Our study also directly demonstrates the functional conservation of the regulatory mechanisms governing Pax6 transcription in teleosts and mammals.

Amacrine Cells/metabolism, Animals, Animals, Genetically Modified, Base Sequence, Chromosomes, Artificial, Bacterial/genetics, Conserved Sequence, DNA Primers/genetics, Evolution, Molecular, Eye Proteins/genetics, Gene Expression Regulation, Developmental, Genes, Reporter, Green Fluorescent Proteins/genetics, Homeodomain Proteins/genetics, Luminescent Proteins/genetics, Mammals/genetics, Mice, Mice, Transgenic, Molecular Sequence Data, Neuroglia/metabolism, PAX6 Transcription Factor, Paired Box Transcription Factors/genetics, Promoter Regions, Genetic, Protein Isoforms/genetics, Recombinant Proteins/genetics, Repressor Proteins/genetics, Retina/cytology, Retinal Bipolar Cells/metabolism, Sequence Homology, Nucleic Acid, Zebrafish/embryology, Zebrafish Proteins/genetics
0012-1606
498-520
Lakowski, Jörn
1856e739-982a-412a-87c7-abf1610f5384
Majumder, Anirban
6601c255-573a-4a2b-ad1d-4b26fab74b19
Lauderdale, James D.
79bd88bf-f7ac-46e0-9c27-efa2739c9b9b
Lakowski, Jörn
1856e739-982a-412a-87c7-abf1610f5384
Majumder, Anirban
6601c255-573a-4a2b-ad1d-4b26fab74b19
Lauderdale, James D.
79bd88bf-f7ac-46e0-9c27-efa2739c9b9b

Lakowski, Jörn, Majumder, Anirban and Lauderdale, James D. (2007) Mechanisms controlling Pax6 isoform expression in the retina have been conserved between teleosts and mammals. Developmental Biology, 307 (2), 498-520. (doi:10.1016/j.ydbio.2007.04.015).

Record type: Article

Abstract

The Pax6 gene plays several roles in retinal development, including control of cell proliferation, maintenance of the retinogenic potential of progenitor cells, and cell fate specification. Emerging evidence suggests that these different aspects of Pax6 gene function are mediated by different isoforms of the Pax6 protein; however, relatively little is known about the spatiotemporal expression of Pax6 isoforms in the vertebrate retina. Using bacterial artificial chromosome (BAC) technology, we modified a zebrafish Pax6a BAC such that we could distinguish paired-containing Pax6a transcripts from paired-less Pax6a transcripts. In the zebrafish, the spatial and temporal onset of expression of these transcripts suggests that the paired-less isoform is involved in the cell fate decision leading to the generation of amacrine cells; however, because of limitations associated with transient transgenic analysis, it was not feasible to establish whether this promoter was active in all amacrine cells or in a specific population of amacrine cells. By making mice transgenic for the zebrafish Pax6a BAC reporter transgene, we were able to show that paired-containing and paired-less Pax6a transcripts were differentially expressed in amacrine subpopulations. Our study also directly demonstrates the functional conservation of the regulatory mechanisms governing Pax6 transcription in teleosts and mammals.

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More information

Published date: 15 July 2007
Keywords: Amacrine Cells/metabolism, Animals, Animals, Genetically Modified, Base Sequence, Chromosomes, Artificial, Bacterial/genetics, Conserved Sequence, DNA Primers/genetics, Evolution, Molecular, Eye Proteins/genetics, Gene Expression Regulation, Developmental, Genes, Reporter, Green Fluorescent Proteins/genetics, Homeodomain Proteins/genetics, Luminescent Proteins/genetics, Mammals/genetics, Mice, Mice, Transgenic, Molecular Sequence Data, Neuroglia/metabolism, PAX6 Transcription Factor, Paired Box Transcription Factors/genetics, Promoter Regions, Genetic, Protein Isoforms/genetics, Recombinant Proteins/genetics, Repressor Proteins/genetics, Retina/cytology, Retinal Bipolar Cells/metabolism, Sequence Homology, Nucleic Acid, Zebrafish/embryology, Zebrafish Proteins/genetics

Identifiers

Local EPrints ID: 431028
URI: http://eprints.soton.ac.uk/id/eprint/431028
ISSN: 0012-1606
PURE UUID: d658ddbc-e176-4784-9498-e058b3472280
ORCID for Jörn Lakowski: ORCID iD orcid.org/0000-0003-4214-7580

Catalogue record

Date deposited: 22 May 2019 16:30
Last modified: 10 Nov 2021 03:50

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Contributors

Author: Jörn Lakowski ORCID iD
Author: Anirban Majumder
Author: James D. Lauderdale

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