PUBLICATION

Distant Insulin Signaling Regulates Vertebrate Pigmentation through the Sheddase Bace2

Authors
Zhang, Y.M., Zimmer, M.A., Guardia, T., Callahan, S.J., Mondal, C., Di Martino, J., Takagi, T., Fennell, M., Garippa, R., Campbell, N.R., Bravo-Cordero, J.J., White, R.M.
ID
ZDB-PUB-180530-27
Date
2018
Source
Developmental Cell   45(5): 580-594.e7 (Journal)
Registered Authors
White, Richard M.
Keywords
PI3K, bace2, insulin, insulin receptor, mTOR, melanocyte, melanophore, pigment patterning, zebrafish
MeSH Terms
  • Cell Movement/physiology
  • Signal Transduction
  • Melanophores/cytology
  • Melanophores/physiology*
  • Pigmentation*
  • Zebrafish/embryology
  • Zebrafish/physiology*
  • TOR Serine-Threonine Kinases/genetics
  • TOR Serine-Threonine Kinases/metabolism
  • Gene Expression Regulation, Developmental
  • Animals
  • Phenotype
  • Mutation
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Insulin/genetics
  • Insulin/metabolism*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/physiology
  • Amyloid Precursor Protein Secretases/genetics
  • Amyloid Precursor Protein Secretases/metabolism*
  • Phosphatidylinositol 3-Kinases
  • Body Patterning*
(all 23)
PubMed
29804876 Full text @ Dev. Cell
Abstract
Patterning of vertebrate melanophores is essential for mate selection and protection from UV-induced damage. Patterning can be influenced by circulating long-range factors, such as hormones, but it is unclear how their activity is controlled in recipient cells to prevent excesses in cell number and migration. The zebrafish wanderlust mutant harbors a mutation in the sheddase bace2 and exhibits hyperdendritic and hyperproliferative melanophores that localize to aberrant sites. We performed a chemical screen to identify suppressors of the wanderlust phenotype and found that inhibition of insulin/PI3Kγ/mTOR signaling rescues the defect. In normal physiology, Bace2 cleaves the insulin receptor, whereas its loss results in hyperactive insulin/PI3K/mTOR signaling. Insulin B, an isoform enriched in the head, drives the melanophore defect. These results suggest that insulin signaling is negatively regulated by melanophore-specific expression of a sheddase, highlighting how long-distance factors can be regulated in a cell-type-specific manner.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu3332
    Point Mutation
    mk207TgTransgenic Insertion
      mk208TgTransgenic Insertion
        mk209
          Unknown
          w47TgTransgenic Insertion
            wprt11TgTransgenic Insertion
              1 - 6 of 6
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              Target Reagent Reagent Type
              bace2MO1-bace2MRPHLNO
              insMO2-insMRPHLNO
              insbMO2-insbMRPHLNO
              insraCRISPR3-insraCRISPR
              insraMO2-insraMRPHLNO
              insrbCRISPR3-insrbCRISPR
              insrbMO2-insrbMRPHLNO
              mnx1MO2-mnx1MRPHLNO
              mtorMO1-mtorMRPHLNO
              pdx1MO1-pdx1MRPHLNO
              1 - 10 of 17
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              Fish
              Antibodies
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              GFPEFGGFP
              mCherryEFGmCherry
              YFPEFGYFP
              1 - 3 of 3
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              Mapping
              No data available