A positive role for Patched in Hedgehog signaling revealed by the intracellular trafficking of Sex-lethal, the<i>Drosophila</i>sex determination master switch

Horabin, Jamila I.; Walthall, Sabrina L.; Vied, Cynthia; Moses, Michelle

doi:10.1242/dev.00865

Cited by 12 publications

(22 citation statements)

References 37 publications

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“…In the anterior compartment of the wing disc, Ptc appears to be a positive effector of this Hh promoted nuclear entry, while Smo has no role (Horabin et al, 2003). Here, it is shown that promotion of Sxl nuclear entry by Hh requires the cholesterol but not palmitoyl modification on Hh.…”

Section: Introductionmentioning

confidence: 69%

“…1B,C,E). The normal high nuclear levels in the posterior compartment and graded nuclear localization in the anterior compartment (Horabin et al, 2003) are detected, with no change in the cells expressing HhN.…”

Section: Resultsmentioning

confidence: 93%

“…Previously, we showed that Hh promotes the nuclear entry of Sxl in both germ cells and somatic cells (Vied and Horabin, 2001;Horabin et al, 2003). In the anterior compartment of the wing disc, Ptc appears to be a positive effector of this Hh promoted nuclear entry, while Smo has no role (Horabin et al, 2003).…”

Section: Introductionmentioning

confidence: 89%

“…Anti-Sal were used at 1:400 and anti-Ptc at 1:5. The rest of the antibodies and staining procedures are described by Horabin et al (Horabin et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

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Splitting the Hedgehog signal: sex and patterning inDrosophila

Horabin

2005

Development

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Sex-lethal (Sxl), the Drosophilasex-determination master switch, is on in females and controls sexual development as a splicing and translational regulator. Hedgehog (Hh) is a secreted protein that specifies cell fate during development. Previous work has demonstrated that Sxl protein is part of the Hh cytoplasmic signaling complex and that Hh promotes Sxl nuclear entry. In the wing disc anterior compartment, Patched (Ptc), the Hh receptor, acts positively in this process. Here, it is shown that the levels and rate of nuclear entry of full-length Cubitus interruptus (Ci), the Hh signaling target, are enhanced by Sxl. This effect requires the cholesterol but not palmitoyl modification on Hh, and expands the zone of full-length Ci expression. Expansion of Ci activation and its downstream targets, particularly decapentaplegic the Drosophila TGFβ homolog, suggests a mechanism for generating different body sizes in the sexes; in Drosophila, females are larger and this difference is controlled by Sxl. Consistent with this proposal, discs expressing ectopic Sxl show an increase in growth. In keeping with the idea of the involvement of a signaling system, this growth effect by Sxl is not cell autonomous. These results have implications for all organisms that are sexually dimorphic and use Hh for patterning.

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Section: Introductionmentioning

confidence: 69%

Section: Resultsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 89%

“…Anti-Sal were used at 1:400 and anti-Ptc at 1:5. The rest of the antibodies and staining procedures are described by Horabin et al (Horabin et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

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Splitting the Hedgehog signal: sex and patterning inDrosophila

Horabin

2005

Development

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“…However, fne null mutants have defects in male courtship behavior [33], suggesting that fne could play a specific role in sexual dimorphism. In addition to its role in RNA regulation, Sxl has also been found to interact with cytoplasmic components of the Hedgehog signaling pathway [34], and a role in regulating stability and nuclear localization of the transcription factor Cubitus interruptus has also been reported [35]. Furthermore, Sxl binds a subunit of RNA polymerase III, suggesting that it may regulate transcription [36].…”

Section: Sxl Acts In Neurons To Remotely Control Ssd Via a Novel Mechmentioning

confidence: 99%

Sex-lethal in neurons controls female body growth inDrosophila

Sawala

Gould

2018

Fly

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Sexual size dimorphism (SSD), a sex difference in body size, is widespread throughout the animal kingdom, raising the question of how sex influences existing growth regulatory pathways to bring about SSD. In insects, somatic sexual differentiation has long been considered to be controlled strictly cell-autonomously. Here, we discuss our surprising finding that in Drosophila larvae, the sex determination gene Sex-lethal (Sxl) functions in neurons to non-autonomously specify SSD. We found that Sxl is required in specific neuronal subsets to upregulate female body growth, including in the neurosecretory insulin producing cells, even though insulin-like peptides themselves appear not to be involved. SSD regulation by neuronal Sxl is also independent of its known splicing targets, transformer and msl-2, suggesting that it involves a new molecular mechanism. Interestingly, SSD control by neuronal Sxl is selective for larval, not imaginal tissue types, and operates in addition to cell-autonomous effects of Sxl and Tra, which are present in both larval and imaginal tissues. Overall, our findings add to a small but growing number of studies reporting non-autonomous, likely hormonal, control of sex differences in Drosophila, and suggest that the principles of sexual differentiation in insects and mammals may be more similar than previously thought.

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Regulation of Hedgehog signaling: a complex story

Ogden

Ascano

Stegman

et al. 2004

Biochemical Pharmacology

102

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The Hedgehog (Hh) signal transduction pathway plays critical instructional roles during development. Activating mutations in human Hh signaling components predispose to a variety of tumor types, and have been observed in sporadic tumors occurring in a wide range of organs. Multiple insights into the regulation of Hh signaling have been achieved through studies using Drosophila melanogaster as a model organism. In Drosophila, regulation of the transcription factor

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A positive role for Patched in Hedgehog signaling revealed by the intracellular trafficking of Sex-lethal, theDrosophilasex determination master switch

Cited by 12 publications

References 37 publications

Splitting the Hedgehog signal: sex and patterning inDrosophila

Splitting the Hedgehog signal: sex and patterning inDrosophila

Sex-lethal in neurons controls female body growth inDrosophila

Regulation of Hedgehog signaling: a complex story

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