CoChat
Sign Up
Cited by 4Developmental Biology and Gene RegulationHippo pathway signaling and YAP/TAZAxon Guidance and Neuronal Signaling

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Contributions of the Dachsous intracellular domain to Dachsous-Fat signaling

Open access
Tripathi, Bipin Kumar, Irvine, Kenneth D.·2024·Development
DOI 10.1242/dev.202919PMC PMC11634027

Published version of a preprint

Open this paper in CoChat — free account

Abstract

The protocadherins Fat and Dachsous regulate organ growth, shape, patterning, and planar cell polarity. Although Dachsous and Fat have been described as ligand and receptor, respectively, in a signal transduction pathway, there is also evidence for bidirectional signaling. Here, we assess signaling downstream of Dachsous through analysis of its intracellular domain. Genomic deletions of conserved sequences within dachsous identified regions of the intracellular domain that contribute to Dachsous activity. Deletion of the A motif increased Dachsous protein levels and decreased wing size. Deletion of the D motif decreased Dachsous levels at cell membranes, increased wing size, and disrupted wing, leg and hindgut patterning and planar cell polarity. Co-immunoprecipitation experiments established that the D motif is necessary and sufficient for association of Dachsous with key partners, including Lowfat, Dachs, Spiny-legs, Fat and MyoID. Subdivision of the D motif identified distinct regions that preferentially contribute to different Dachsous activities. Our results identify motifs that are essential for Dachsous function and are consistent with the hypothesis that the key function of Dachsous is regulation of Fat.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1242/dev.202919

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 66

  1. Adler, 1998, Mutations in the cadherin superfamily member gene dachsous cause a tissue polarity phenotype by altering frizzled signaling, Development, 125, 959, 10.1242/dev.125.5.959 · DOI
  2. Alders, 2014, Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome, Hum. Genet., 133, 1161, 10.1007/s00439-014-1456-y · DOI
  3. Ambegaonkar, 2015, Coordination of planar cell polarity pathways through Spiny-legs, eLife, 4, e09946, 10.7554/eLife.09946 · DOI
  4. Ambegaonkar, 2012, Propagation of Dachsous-Fat planar cell polarity, Curr. Biol., 22, 1302, 10.1016/j.cub.2012.05.049 · DOI
  5. Ayukawa, 2014, Dachsous-dependent asymmetric localization of spiny-legs determines planar cell polarity orientation in Drosophila, Cell Rep., 8, 609, 10.1016/j.celrep.2014.06.009 · DOI
  6. Baena-López, 2005, The orientation of cell divisions determines the shape of Drosophila organs, Curr. Biol., 15, 1640, 10.1016/j.cub.2005.07.062 · DOI
  7. Bennett, 2006, Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway, Curr. Biol., 16, 2101, 10.1016/j.cub.2006.09.045 · DOI
  8. Bosveld, 2012, Mechanical control of morphogenesis by Fat/Dachsous/Four-jointed planar cell polarity pathway, Science, 336, 724, 10.1126/science.1221071 · DOI
  9. Brittle, 2010, Four-jointed modulates growth and planar polarity by reducing the affinity of dachsous for fat, Curr. Biol., 20, 803, 10.1016/j.cub.2010.03.056 · DOI
  10. Brittle, 2012, Planar polarity specification through asymmetric subcellular localization of Fat and Dachsous, Curr. Biol., 22, 907, 10.1016/j.cub.2012.03.053 · DOI
  11. Bryant, 1988, Mutations at the fat locus interfere with cell proliferation control and epithelial morphogenesis in Drosophila, Dev. Biol., 129, 541, 10.1016/0012-1606(88)90399-5 · DOI
  12. Cappello, 2013, Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development, Nat. Genet., 45, 1300, 10.1038/ng.2765 · DOI
  13. Casal, 2006, Two separate molecular systems, Dachsous/Fat and Starry night/Frizzled, act independently to confer planar cell polarity, Development, 133, 4561, 10.1242/dev.02641 · DOI
  14. Chen, 2024, Atypical cadherin Dachsous1b interacts with Ttc28 and Aurora B to control microtubule dynamics in embryonic cleavages, Dev. Cell, 45, 376, 10.1016/j.devcel.2018.04.009 · DOI
  15. Cho, 2004, Action of fat, four-jointed, dachsous and dachs in distal-to-proximal wing signaling, Development, 131, 4489, 10.1242/dev.01315 · DOI
  16. Cho, 2006, Delineation of a Fat tumor suppressor pathway, Nat. Genet., 38, 1142, 10.1038/ng1887 · DOI
  17. Clark, 1995, Dachsous encodes a member of the cadherin superfamily that controls imaginal disc morphogenesis in Drosophila, Genes Dev., 9, 1530, 10.1101/gad.9.12.1530 · DOI
  18. Degoutin, 2013, Riquiqui and minibrain are regulators of the hippo pathway downstream of Dachsous, Nat. Cell Biol., 15, 1176, 10.1038/ncb2829 · DOI
  19. Durst, 2015, Mutations in DCHS1 cause mitral valve prolapse, Nature, 525, 109, 10.1038/nature14670 · DOI
  20. Feng, 2009, Processing and phosphorylation of the Fat receptor, Proc. Natl. Acad. Sci. USA, 106, 11989, 10.1073/pnas.0811540106 · DOI
  21. Feng, 2007, Fat and Expanded act in parallel to regulate growth through Warts, Proc. Natl. Acad. Sci. USA, 104, 20362, 10.1073/pnas.0706722105 · DOI
  22. Fulford, 2020, Fat/Dachsous family cadherins in cell and tissue organisation, Curr. Opin. Cell Biol., 62, 96, 10.1016/j.ceb.2019.10.006 · DOI
  23. Fulford, 2023, Expanded directly binds conserved regions of Fat to restrain growth via the Hippo pathway, J. Cell Biol., 222, e202204059, 10.1083/jcb.202204059 · DOI
  24. González-Morales, 2015, The atypical cadherin Dachsous controls left-right asymmetry in Drosophila, Dev. Cell, 33, 675, 10.1016/j.devcel.2015.04.026 · DOI
  25. Götzke, 2019, The ALFA-tag is a highly versatile tool for nanobody-based bioscience applications, Nat. Commun., 10, 4403, 10.1038/s41467-019-12301-7 · DOI
  26. Gramates, 2022, FlyBase: a guided tour of highlighted features, Genetics, 220, iyac035, 10.1093/genetics/iyac035 · DOI
  27. Gridnev, 2022, Emerging mechanisms of growth and patterning regulation by Dachsous and fat Protocadherins, Front. Cell Dev. Biol., 10, 842593, 10.3389/fcell.2022.842593 · DOI
  28. Gubb, 1999, The balance between isoforms of the prickle LIM domain protein is critical for planar polarity in Drosophila imaginal discs, Genes Dev., 13, 2315, 10.1101/gad.13.17.2315 · DOI
  29. Hozumi, 2006, An unconventional myosin in Drosophila reverses the default handedness in visceral organs, Nature., 440, 798, 10.1038/nature04625 · DOI
  30. Ishikawa, 2008, Four-jointed is a Golgi kinase that phosphorylates a subset of cadherin domains, Science, 321, 401, 10.1126/science.1158159 · DOI
  31. Jenkins, 2022, Using FlyBase: a database of Drosophila genes and genetics, Methods Mol. Biol., 2540, 1, 10.1007/978-1-0716-2541-5_1 · DOI
  32. Juan, 2018, Myosin1D is an evolutionarily conserved regulator of animal left-right asymmetry, Nat. Commun., 9, 1942, 10.1038/s41467-018-04284-8 · DOI
  33. Ma, 2003, Fidelity in planar cell polarity signalling, Nature, 421, 543, 10.1038/nature01366 · DOI
  34. Madeira, 2022, Search and sequence analysis tools services from EMBL-EBI in 2022, Nucleic Acids Res., 50, W276, 10.1093/nar/gkac240 · DOI
  35. Mahoney, 1991, The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily, Cell, 67, 853, 10.1016/0092-8674(91)90359-7 · DOI
  36. Mao, 2006, Dachs: an unconventional myosin that functions downstream of Fat to regulate growth, affinity and gene expression in Drosophila, Development, 133, 2539, 10.1242/dev.02427 · DOI
  37. Mao, 2009, Drosophila lowfat, a novel modulator of Fat signaling, Development, 136, 3223, 10.1242/dev.036152 · DOI
  38. Mao, 2011, Characterization of a Dchs1 mutant mouse reveals requirements for Dchs1-Fat4 signaling during mammalian development, Development, 138, 947, 10.1242/dev.057166 · DOI
  39. Matakatsu, 2004, Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing, Development, 131, 3785, 10.1242/dev.01254 · DOI
  40. Matakatsu, 2006, Separating the adhesive and signaling functions of the Fat and Dachsous protocadherins, Development, 133, 2315, 10.1242/dev.02401 · DOI
  41. Matakatsu, 2012, Separating planar cell polarity and Hippo pathway activities of the protocadherins Fat and Dachsous, Development, 139, 1498, 10.1242/dev.070367 · DOI
  42. Merkel, 2014, The balance of prickle/spiny-legs isoforms controls the amount of coupling between core and fat PCP systems, Curr. Biol., 24, 2111, 10.1016/j.cub.2014.08.005 · DOI
  43. Misra, 2016, Vamana couples fat signaling to the Hippo pathway, Dev. Cell, 39, 254, 10.1016/j.devcel.2016.09.017 · DOI
  44. Olofsson, 2014, Prickle/spiny-legs isoforms control the polarity of the apical microtubule network in planar cell polarity, Development, 141, 2866, 10.1242/dev.105932 · DOI
  45. Pan, 2013, Signal transduction by the Fat cytoplasmic domain, Development, 140, 831, 10.1242/dev.088534 · DOI
  46. Rauskolb, 2019, Localization of Hippo signaling components in drosophila by fluorescence and immunofluorescence, Methods Mol. Biol., 1893, 61, 10.1007/978-1-4939-8910-2_5 · DOI
  47. Rodriguez, 2004, The dachsous gene, a member of the cadherin family, is required for Wg-dependent pattern formation in the Drosophila wing disc, Development, 131, 3195, 10.1242/dev.01195 · DOI
  48. Rogulja, 2008, Morphogen control of wing growth through the Fat signaling pathway, Dev. Cell, 15, 309, 10.1016/j.devcel.2008.06.003 · DOI
  49. Saburi, 2008, Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease, Nat. Genet., 40, 1010, 10.1038/ng.179 · DOI
  50. Saydmohammed, 2018, Vertebrate myosin 1d regulates left-right organizer morphogenesis and laterality, Nat. Commun., 9, 3381, 10.1038/s41467-018-05866-2 · DOI
  51. Schindelin, 2012, Fiji: an open-source platform for biological-image analysis, Nat. Methods, 9, 676, 10.1038/nmeth.2019 · DOI · Paper page
  52. Silva, 2006, The tumor-suppressor gene fat controls tissue growth upstream of expanded in the Hippo signaling pathway, Curr. Biol., 16, 2081, 10.1016/j.cub.2006.09.004 · DOI
  53. Simon, 2010, Modulation of fat:dachsous binding by the cadherin domain kinase four-jointed, Curr. Biol., 20, 811, 10.1016/j.cub.2010.04.016 · DOI
  54. Strutt, 2002, Nonautonomous planar polarity patterning in Drosophila: dishevelled-independent functions of frizzled, Dev. Cell, 3, 851, 10.1016/S1534-5807(02)00363-5 · DOI
  55. Strutt, 2021, How do the Fat-Dachsous and core planar polarity pathways act together and independently to coordinate polarized cell behaviours?, Open Biol., 11, 200356, 10.1098/rsob.200356 · DOI
  56. Villano, 1995, four-jointed is required for intermediate growth in the proximal-distal axis in Drosophila, Development, 121, 2767, 10.1242/dev.121.9.2767 · DOI
  57. Vrabioiu, 2015, Fat/Dachsous signaling promotes Drosophila wing growth by regulating the conformational state of the NDR kinase warts, Dev. Cell, 35, 737, 10.1016/j.devcel.2015.11.027 · DOI
  58. Wang, 2019, Fat-regulated adaptor protein Dlish binds the growth suppressor Expanded and controls its stability and ubiquitination, Proc. Natl. Acad. Sci. USA, 116, 1319, 10.1073/pnas.1811891116 · DOI
  59. Waterhouse, 2009, Jalview Version 2--a multiple sequence alignment editor and analysis workbench, Bioinformatics, 25, 1189, 10.1093/bioinformatics/btp033 · DOI
  60. Willecke, 2006, The fat cadherin acts through the Hippo tumor-suppressor pathway to regulate tissue size, Curr. Biol., 16, 2090, 10.1016/j.cub.2006.09.005 · DOI
  61. Willecke, 2008, Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation, Proc. Natl. Acad. Sci. USA, 105, 14897, 10.1073/pnas.0805201105 · DOI
  62. Yang, 2002, Regulation of Frizzled by fat-like cadherins during planar polarity signaling in the Drosophila compound eye, Cell, 108, 675, 10.1016/S0092-8674(02)00658-X · DOI
  63. Zakaria, 2014, Regulation of neuronal migration by Dchs1-Fat4 planar cell polarity, Curr. Biol., 24, 1620, 10.1016/j.cub.2014.05.067 · DOI
  64. Zhang, 2014, A versatile two-step CRISPR- and RMCE-based strategy for efficient genome engineering in Drosophila, G3 (Bethesda), 4, 2409, 10.1534/g3.114.013979 · DOI
  65. Zhang, 2016, The novel SH3 domain protein Dlish/CG10933 mediates fat signaling in Drosophila by binding and regulating Dachs, eLife, 5, e16624, 10.7554/eLife.16624 · DOI
  66. Zhao, 2013, The Drosophila Cadherin Fat regulates tissue size and planar cell polarity through different domains, PLoS ONE, 8, e62998, 10.1371/journal.pone.0062998 · DOI

Metadata

Authors
Tripathi, B. K., & Irvine, K. D.
Affiliations
Rutgers, The State University of New Jersey (US)
Corresponding author
Irvine, Kenneth D.
ORCID
Venue
Development
Publisher
The Company of Biologists
Published
2024-11-29
Volume
151
Issue
23
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.202919
PMC
PMC11634027
OpenAlex
W4404112806
Cited by
4
References
2
Citations by year
2026: 2 · 2025: 2
FWCI
0.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Development (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health (GM131748)
  • Rutgers, The State University of New Jersey
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
Dachsous, fats, protocadherins, cytoplasmic domain, planar cell polarity, wing patterning, organ growth, DACH, bidirectional signaling, Drosophila

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review