Hedgehog and extramacrochaetae in the<i>Drosophila</i>eye

Spratford, Carrie M.; Kumar, Justin P.

doi:10.4161/fly.27691

Cited by 6 publications

(2 citation statements)

References 42 publications

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“…This leads to furrow progression across the eye disc and determines the number of ommatidia in the adult eye ( Ma et al, 1993 ). Accordingly, reduced Hh production in flies lacking most endogenous Hh production in the eye disc (in a hh bar 3 /hh AC background) delays furrow progression and results in significantly fewer ommatidia (114 ± 19 in female flies at 18°C, Figures 1A,C ) than in wild-type eyes (664 ± 35 ommatidia in female flies; P < 0.001, Figures 1A,B ; Spratford and Kumar, 2014 ).…”

Section: Resultsmentioning

confidence: 96%

C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation

Manikowski

Kastl

Schürmann

et al. 2021

Front. Cell Dev. Biol.

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Hedgehog (Hh) morphogens are involved in embryonic development and stem cell biology and, if misregulated, can contribute to cancer. One important post-translational modification with profound impact on Hh biofunction is its C-terminal cholesteroylation during biosynthesis. The current hypothesis is that the cholesterol moiety is a decisive factor in Hh association with the outer plasma membrane leaflet of producing cells, cell-surface Hh multimerization, and its transport and signaling. Yet, it is not decided whether the cholesterol moiety is directly involved in all of these processes, because their functional interdependency raises the alternative possibility that the cholesterol initiates early processes directly and that these processes can then steer later stages of Hh signaling independent of the lipid. We generated variants of the C-terminal Hh peptide and observed that these cholesteroylated peptides variably impaired several post-translational processes in producing cells and Hh biofunction in Drosophila melanogaster eye and wing development. We also found that substantial Hh amounts separated from cholesteroylated peptide tags in vitro and in vivo and that tagged and untagged Hh variants lacking their C-cholesterol moieties remained bioactive. Our approach thus confirms that Hh cholesteroylation is essential during the early steps of Hh production and maturation but also suggests that it is dispensable for Hh signal reception at receiving cells.

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Section: Resultsmentioning

confidence: 96%

C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation

Manikowski

Kastl

Schürmann

et al. 2021

Front. Cell Dev. Biol.

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“…Wandering third instar larval eye–antennal disk complexes were prepared as described ( Spratford and Kumar 2014 ). They were then incubated in rat α-HA at 1:500 overnight at 4°C (Roche 3F10; Sigma-Aldrich, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Fourth Chromosome Resource Project: a comprehensive resource for genetic analysis in Drosophila that includes humanized stocks

Stinchfield,

Weasner,

Weasner

et al. 2023

Genetics

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The fourth chromosome is the final frontier for genetic analysis in Drosophila. Small, heterochromatic, and devoid of recombination the fourth has long been ignored. Nevertheless, its long arm contains 79 protein-coding genes. The Fourth Chromosome Resource Project (FCRP) has a goal of facilitating the investigation of genes on this neglected chromosome. The project has 446 stocks publicly available at the Bloomington and Kyoto stock centers with phenotypic data curated by the FlyBase and FlyPush resources. Four of the five stock sets are nearly complete: (1) UAS.fly cDNAs, (2) UAS.human homolog cDNAs, (3) gene trap mutants and protein traps, and (4) stocks promoting meiotic and mitotic recombination on the fourth. Ongoing is mutagenesis of each fourth gene on a new FRT-bearing chromosome for marked single-cell clones. Beyond flies, FCRP facilitates the creation and analysis of humanized fly stocks. These provide opportunities to apply Drosophila genetics to the analysis of human gene interaction and function. In addition, the FCRP provides investigators with confidence through stock validation and an incentive via phenotyping to tackle genes on the fourth that have never been studied. Taken together, FCRP stocks will facilitate all manner of genetic and molecular studies. The resource is readily available to researchers to enhance our understanding of metazoan biology, including conserved molecular mechanisms underlying health and disease.

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The fly eye: Through the looking glass

Kumar

2017

Developmental Dynamics

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The developing eye-antennal disc of Drosophila melanogaster has been studied for more than a century, and it has been used as a model system to study diverse processes, such as tissue specification, organ growth, programmed cell death, compartment boundaries, pattern formation, cell fate specification, and planar cell polarity. The findings that have come out of these studies have informed our understanding of basic developmental processes as well as human disease. For example, the isolation of a white-eyed fly ultimately led to a greater appreciation of the role that sex chromosomes play in development, sex determination, and sex linked genetic disorders. Similarly, the discovery of the Sevenless receptor tyrosine kinase pathway not only revealed how the fate of the R7 photoreceptor is selected but it also helped our understanding of how disruptions in similar biochemical pathways result in tumorigenesis and cancer onset. In this article, I will discuss some underappreciated areas of fly eye development that are fertile for investigation and are ripe for producing exciting new breakthroughs. The topics covered here include organ shape, growth control, inductive signaling, and right-left symmetry. Developmental Dynamics 247:111-123, 2018. © 2017 Wiley Periodicals, Inc.

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Hedgehog and extramacrochaetae in theDrosophilaeye

Cited by 6 publications

References 42 publications

C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation

C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation

Fourth Chromosome Resource Project: a comprehensive resource for genetic analysis in Drosophila that includes humanized stocks

The fly eye: Through the looking glass

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