A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development
Year: 2017
Type: article
Abstract: The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation.
Source: eLife
DOI: 10.7554/elife.29145
Institutions: Boston Children's Hospital, Howard Hughes Medical Institute, Harvard University, Washington University in St. Louis, Massachusetts General Hospital, Royal Netherlands Academy of Arts and Sciences, University Medical Center Utrecht, Hubrecht Institute for Developmental Biology and Stem Cell Research, Harvard Stem Cell Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Howard Hughes Medical Institute, Melanoma Research Alliance, Lawrence Ellison Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research
OpenAlex ID: W2747950677