Pph13 and orthodenticle define a dual regulatory pathway for photoreceptor cell morphogenesis and function
Open accessAbstract
The function and integrity of photoreceptor cells are dependent upon the creation and maintenance of specialized apical structures: membrane discs/outer segments in vertebrates and rhabdomeres in insects. We performed a molecular and morphological comparison of Drosophila Pph13 and orthodenticle (otd) mutants to investigate the transcriptional network controlling the late stages of rhabdomeric photoreceptor cell development and function. Although Otd and Pph13 have been implicated in rhabdomere morphogenesis, we demonstrate that it is necessary to remove both factors to completely eliminate rhabdomere formation. Rhabdomere absence is not the result of degeneration or a failure of initiation, but rather the inability of the apical membrane to transform and elaborate into a rhabdomere. Transcriptional profiling revealed that Pph13 plays an integral role in promoting rhabdomeric photoreceptor cell function. Pph13 regulates Rh2 and Rh6, and other phototransduction genes, demonstrating that Pph13 and Otd control a distinct subset of Rhodopsin-encoding genes in adult visual systems. Bioinformatic, DNA binding and transcriptional reporter assays showed that Pph13 can bind and activate transcription via a perfect Pax6 homeodomain palindromic binding site and the Rhodopsin core sequence I (RCSI) found upstream of Drosophila Rhodopsin genes. In vivo studies indicate that Pph13 is necessary and sufficient to mediate the expression of a multimerized RCSI reporter, a marker of photoreceptor cell specificity previously suggested to be regulated by Pax6. Our studies define a key transcriptional regulatory pathway that is necessary for late Drosophila photoreceptor development and will serve as a basis for better understanding rhabdomeric photoreceptor cell development and function.
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Ocular photoreceptor cells are a pan-bilaterian cell type in which the Box IV GRN controlling receptor subtypes operates downstream of K50 homeodomain family regulatory genes.
“Ocular photoreceptor cells provide another example of a pan-bilaterian cell type in which the Box IV GRN controlling the various subtypes of receptors (rhabdomeric receptors in insects, and rods and cones in vertebrates) operate downstream of regulatory genes of the K50 homeodomain family (Mishra et al., 2010; Ranade et al., 2008).”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Mishra et al., 2010
The Introduction (p. 2) identifies Otd as a K50-family factor and draws a parallel with vertebrate Crx. The Results (pp. 6–7) show that Otd regulates some Drosophila rhodopsins, but others depend on Pph13, a Q50 factor. The paper does not establish that a Box IV network controlling receptor subtypes operates downstream of K50 genes across bilaterians. (LLM, conf=0.86)
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Evolution of Gene Regulatory Networks Controlling Body Plan Development
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- Authors
- Mishra, M., Oke, A., Lebel, C., McDonald, E. C., Plummer, Z., Cook, T. A., & Zelhof, A. C.
- Affiliations
- Indiana University Bloomington (US)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Zelhof, Andrew C.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2010-09-01
- Volume
- 137
- Issue
- 17
- Pages
- 2895-2904
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2938920
- OpenAlex
- W2108165551
- Cited by
- 65
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 1 · 2018: 2 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 9 · 2012: 9
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute (R01EY017907)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD046387)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- orthodenticle, photoreceptor development, Drosophila, transcriptional regulation, rhodopsin gene, Rh2, phototransduction, transcriptional activation
- MeSH terms
- Animals, Base Sequence, Binding Sites, DNA, Drosophila melanogaster, Mutation, Promoter Regions, Genetic, Rhodopsin, Genes, Insect, Photoreceptor Cells, Invertebrate, Homeodomain Proteins, Gene Expression Regulation, Developmental, Gene Expression Profiling, Drosophila Proteins, Animals, Genetically Modified, Microscopy, Electron, Transmission
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