Title | Distant Insulin Signaling Regulates Vertebrate Pigmentation through the Sheddase Bace2. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Zhang YM, Zimmer MA, Guardia T, Callahan SJ, Mondal C, Di Martino J, Takagi T, Fennell M, Garippa R, Campbell NR, Bravo-Cordero JJavier, White RM |
Journal | Dev Cell |
Volume | 45 |
Issue | 5 |
Pagination | 580-594.e7 |
Date Published | 2018 06 04 |
ISSN | 1878-1551 |
Keywords | Amyloid Precursor Protein Secretases, Animals, Body Patterning, Cell Movement, Embryo, Nonmammalian, Gene Expression Regulation, Developmental, Insulin, Melanophores, Mutation, Phenotype, Phosphatidylinositol 3-Kinases, Pigmentation, Signal Transduction, TOR Serine-Threonine Kinases, Zebrafish, Zebrafish Proteins |
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. |
DOI | 10.1016/j.devcel.2018.04.025 |
Alternate Journal | Dev. Cell |
PubMed ID | 29804876 |
PubMed Central ID | PMC5991976 |
Grant List | R25 GM055036 / GM / NIGMS NIH HHS / United States DP2 CA186572 / CA / NCI NIH HHS / United States F30 CA220954 / CA / NCI NIH HHS / United States K08 AR055368 / AR / NIAMS NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States K22 CA196750 / CA / NCI NIH HHS / United States F99 CA212436 / CA / NCI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States P30 CA196521 / CA / NCI NIH HHS / United States F31 CA196305 / CA / NCI NIH HHS / United States |
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