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
-
- Amyloid Precursor Protein Secretases/genetics
- Amyloid Precursor Protein Secretases/metabolism*
- Animals
- Body Patterning*
- Cell Movement/physiology
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/physiology
- Gene Expression Regulation, Developmental
- Insulin/genetics
- Insulin/metabolism*
- Melanophores/cytology
- Melanophores/physiology*
- Mutation
- Phenotype
- Phosphatidylinositol 3-Kinases
- Pigmentation*
- Signal Transduction
- TOR Serine-Threonine Kinases/genetics
- TOR Serine-Threonine Kinases/metabolism
- Zebrafish/embryology
- Zebrafish/physiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 29804876 Full text @ Dev. Cell
Citation
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. (2018) Distant Insulin Signaling Regulates Vertebrate Pigmentation through the Sheddase Bace2. Developmental Cell. 45(5):580-594.e7.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping