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Cited by 40Retinal Development and DisordersDevelopmental Biology and Gene RegulationOcular Disorders and Treatments

Otx but not mitf transcription factors are required for zebrafish retinal pigment epithelium development

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Lane, Brandon M., Lister, James A.·2012·PLoS ONE
DOI 10.1371/journal.pone.0049357PMC PMC3489725
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Abstract

Otx and Mitf transcription factors have been implicated in the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific roles in the development of the RPE have not been fully defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2) and two Mitf transcription factors (Mitfa and Mitfb) in the development of the zebrafish RPE was explored in these experiments. The loss of Otx activity through morpholino knockdown produced variable eye defects, ranging from delayed RPE pigmentation to severe coloboma, depending on the combination of Otx factors that were targeted. Expression analysis through in situ hybridization demonstrates that otx transcription factors are necessary for the proper expression of mitfa and mitfb while Mitf transcription factors are not required for the expression of otx genes. Surprisingly, the loss of Mitf activity in mitfa, mitfb, or double mitf mutant zebrafish had no effect on RPE pigmentation or development. Moreover, histological analysis revealed that retinal lamination is unaffected in mitf mutants, as well as in otx morphants, even in regions lacking RPE. Otx and Mitf combined loss of function experiments suggest that mitfa and mitfb may still influence zebrafish RPE development. This is further supported by the ability of mitfa to induce pigmentation in the zebrafish retina when misexpressed. These findings suggest that one or more Otx targets in addition to mitfa and mitfb, possibly another mitf family member, are necessary for development of the RPE in zebrafish.

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Authors
Lane, B. M., & Lister, J. A.
Affiliations
Virginia Commonwealth University (US)
Corresponding author
Lister, James A.
ORCID
Lane, Brandon M.
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2012-11-05
Volume
7
Issue
11
Pages
e49357
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0049357
PMC
PMC3489725
OpenAlex
W2040660031
Cited by
40
References
0
Citations by year
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FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Thomas F. and Kate Miller Jeffress Memorial Trust
  • European Commission
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Ocular Disorders and Treatments
Keywords
mitfa, Otx2, coloboma, retinal lamination, morpholino knockdown, zebrafish eye development, transcriptional regulation
MeSH terms
Animals, Embryo, Nonmammalian, Mutation, Phenotype, Pigmentation, Transcription Factors, Zebrafish, Gene Expression Regulation, Developmental, Cell Lineage, Zebrafish Proteins, Retinal Pigment Epithelium, Gene Knockdown Techniques, Morpholinos

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