title: GLUT3 gene expression is critical for embryonic growth, brain development and survival.
abstract: Glucose is the primary energy source for eukaryotic cells and the predominant substrate for the brain. GLUT3 is essential for trans-placental glucose transport and highly expressed in the mammalian brain. To further elucidate the role of GLUT3 in embryonic development, we utilized the vertebrate whole animal model system of Danio rerio as a tractable system for defining the cellular and molecular mechanisms altered by impaired glucose transport and metabolism related to perturbed expression of GLUT3. The comparable orthologue of human GLUT3 was identified and the expression of this gene abrogated during early embryonic development. In a dose-dependent manner embryonic brain development was disrupted resulting in a phenotype of aberrant brain organogenesis, associated with embryonic growth restriction and increased cellular apoptosis. Rescue of the morphant phenotype was achieved by providing exogenous GLUT3 mRNA. We conclude that GLUT3 is critically important for brain organogenesis and embryonic growth. Disruption of GLUT3 is responsible for the phenotypic spectrum of embryonic growth restriction to demise and neural apoptosis with microcephaly.
authors: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
authors: Mary O
authors: MO
authors: Carayannopoulos
authors: Department of Pediatrics, Division of Neonatology and Developmental Biology, Neonatal Research Center at the UCLA Children's Discovery & Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA, USA.
authors: Fuxia
authors: F
authors: Xiong
authors: Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
authors: Penny
authors: P
authors: Jensen
authors: Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA.
authors: Yesenia
authors: Y
authors: Rios-Galdamez
authors: Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA.
authors: Haigen
authors: H
authors: Huang
authors: Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA.
authors: Shuo
authors: S
authors: Lin
authors: Department of Pediatrics, Division of Neonatology and Developmental Biology, Neonatal Research Center at the UCLA Children's Discovery & Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA, USA. Electronic address: sdevaskar@mednet.ucla.edu.
authors: Sherin U
authors: SU
authors: Devaskar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051274:Glucose Transporter Type 3 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D051274:Glucose Transporter Type 3; D012333:RNA, Messenger; D029961:Zebrafish Proteins
keywords: Apoptosis; Embryonic growth restriction; Microcephaly