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*
- 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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping