OSCR

Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila.

Overview

Authors: Shelley B Gibson1,2, Samantha L Deal3, Ye-Jin Park1,2,4,5, Bo Sun1,5, Yanyan Qi1,5, Jung-Wan Mok1,2, Hyung-Lok Chung6, Hongjie Li1,5, Shinya Yamamoto1,2,4,7
ORCID iDs: Shelley B Gibson, Ye-Jin Park, Bo Sun, Jung-Wan Mok, Hyung-Lok Chung, Shinya Yamamoto
  1. Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas, United States of America
  2. Jan and Dan Duncan Neurological Research Institute (NRI), Texas Children’s Hospital (TCH), Houston, Texas, United States of America
  3. Department of Biology, College of Liberal Arts & Sciences, Mercer University, Macon, Georgia, United States of America
  4. Development, Disease Models & Therapeutics Graduate Program, BCM, Houston, Texas, United States of America
  5. Huffington Center on Aging, BCM, Houston, Texas, United States of America
  6. Department of Neurology, Houston Methodist Research Institute, Houston, Texas, United States of America
  7. Department of Neuroscience, BCM, Houston, Texas, United States of America
Institutions: Baylor College of Medicine (United States); Texas Children's Hospital (United States); Mercer University (United States); Houston Methodist (United States)
Journal: PLoS genetics, volume 22, issue 8, article e1012260
Dates: received 23 December 2025; accepted 20 July 2026; published online 21 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1371/journal.pgen.1012260 · PMID 42627852 · PMCID PMC13524344 · OpenAlex W7203871341
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), drosophila (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Machine learning, Evoked potentials
MeSH: Dopamine*, Drosophila melanogaster*, Drosophila Proteins*, Intracellular Signaling Peptides and Proteins*, Pigmentation*, Protein Serine-Threonine Kinases*, Animals, Dopa Decarboxylase, Dopaminergic Neurons, Hippo Kinases, Humans, Melanins, Melanogenesis, Signal Transduction, Tyrosine 3-Monooxygenase (* major topic)
Topic: Hippo pathway signaling and YAP/TAZ (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Office of Research Infrastructure Programs, National Institutes of Health (S10OD036336, R24OD0022005); NCI NIH HHS (P30 CA125123); The Cullen Foundation (N/A (Predoctoral Fellowship)); National Cancer Institute (P30CA125123); NIH HHS (S10 OD036336, R24 OD022005); Cancer Prevention and Research Institute of Texas (CPRIT-RP240432); Texas Children's Hospital (N/A (NRI Fellowship)); Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083092); Baylor College of Medicine (N/A (SEED funds)); NICHD NIH HHS (U54 HD083092)
Citations: not cited yet (Europe PMC); 160 references in the paper

Abstract

Pigmentation plays multiple important roles in development, physiology and evolution. Melanization of the insect cuticle requires dopamine as a precursor of melanin and involves key enzymes in dopamine biosynthesis including Tyrosine hydroxylase (TH) and Dopa decarboxylase (Ddc). Some studies have hinted that disruption of the evolutionarily conserved Hippo signaling pathway, which has been primarily studied in the context of tissue growth, may lead to changes in cuticle pigmentation in the fruit fly Drosophila melanogaster. However, to our knowledge, there have not been any systematic investigations into their potential mechanistic links. In this study, we identified that all genes that comprise the canonical Hippo signaling pathway [hippo (hpo), salvador (sav), mats, warts (wts), yorkie (yki) and scalloped (sd)] are involved in cuticle pigmentation in the fly notum based on tissue-specific gene knock-down/out experiments and epistatic analysis. Despite the notable divergence of pigmentation mechanisms between invertebrates and vertebrates, these phenotypes can often be rescued by the human orthologs of corresponding fly genes. While we find that manipulation of Hippo signaling in dopaminergic neurons does not affect global dopamine levels in the fly brain, developmental inhibition of this pathway can increase dopamine levels in the fly head, indicating that the mechanism by which dopamine levels are regulated in the nervous system is distinct from that in epithelial cells. Through single nuclei RNA sequencing of the developing fly nota and subsequent functional studies of differentially expressed genes that are altered upon inhibition of Hippo signaling, we found many genes that contribute to cuticle pigmentation downstream of Hippo signaling. We conclude that regulation of cuticle pigmentation by canonical Hippo signaling acts through multiple downstream genes rather than directly through TH and Ddc. We also propose that the Drosophila melanogaster cuticle may serve as a useful platform to identify previously uncharacterized mediators of Hippo signaling as well as an in vivo experimental system to test the functionality of rare genetic variants found in human Hippo signaling orthologs associated with a variety of diseases.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data Availability

Regarding the snRNA-seq experiment, Raw FASTQ files, expression matrix, and processed h5ad files, including cell type annotations, are available at NCBI/GEO (accession number GEO: GSE310450). All other data are included in this manuscript and supplemental information.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 15 MeSH terms, 10 funders, 158 references.

Cite

This paper

Gibson, S. B., Deal, S. L., Park, Y.-J., Sun, B., Qi, Y., Mok, J.-W., Chung, H.-L., Li, H., & Yamamoto, S. (2026). Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila. PLoS genetics, 22(8), e1012260. https://doi.org/10.1371/journal.pgen.1012260

BibTeX

@article{gibson2026hippo,
author = {Gibson, Shelley B and Deal, Samantha L and Park, Ye-Jin and Sun, Bo and Qi, Yanyan and Mok, Jung-Wan and Chung, Hyung-Lok and Li, Hongjie and Yamamoto, Shinya},
title = {{Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila}},
journal = {PLoS genetics},
year = {2026},
month = aug,
volume = {22},
number = {8},
pages = {e1012260},
publisher = {PLOS},
issn = {1553-7390},
doi = {10.1371/journal.pgen.1012260},
url = {https://doi.org/10.1371/journal.pgen.1012260},
pmid = {42627852},
pmcid = {PMC13524344}
}

RIS

TY - JOUR
AU - Gibson, Shelley B
AU - Deal, Samantha L
AU - Park, Ye-Jin
AU - Sun, Bo
AU - Qi, Yanyan
AU - Mok, Jung-Wan
AU - Chung, Hyung-Lok
AU - Li, Hongjie
AU - Yamamoto, Shinya
TI - Hippo signaling regulates cuticle pigmentation and dopamine metabolism in Drosophila
T2 - PLoS genetics
J2 - PLoS Genet
PY - 2026
DA - 2026/08/21
VL - 22
IS - 8
SP - e1012260
SN - 1553-7390
PB - PLOS
DO - 10.1371/journal.pgen.1012260
UR - https://doi.org/10.1371/journal.pgen.1012260
LA - en
ER -

CSL-JSON

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