title: GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish.
abstract: Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 (glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: Marín-Juez
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Rovira
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Crespo
authors.affiliation: Department of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: van der Vaart
authors.affiliation: Department of Molecular Cell Biology, Institute of Biology, Leiden University, Leiden, The Netherlands.
authors.forename: Herman P
authors.initials: HP
authors.lastname: Spaink
authors.affiliation: Departament de Fisiologia i Immunologia, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
authors.forename: Josep V
authors.initials: JV
authors.lastname: Planas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism
chemical_list: D051273:Glucose Transporter Type 2; D005947:Glucose