GLUT3 gene expression is critical for embryonic growth, brain development and survival
GLUT3 gene expression is critical for embryonic growth, brain development and survival
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DOI：
10.1016/j.ymgme.2014.01.013
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发表时间：
2014-04-01
影响因子：
3.8
通讯作者：
Devaskar, Sherin U.
中科院分区：
文献类型：
--
作者：
Carayannopoulos, Mary O.;Xiong, Fuxia;Devaskar, Sherin U.
葡萄糖是真核细胞的主要能量来源，也是大脑的主要底物。GLUT3是跨胎盘葡萄糖转运所必需的，并且在哺乳动物脑中高度表达。为了进一步阐明GLUT3在胚胎发育中的作用，我们利用斑马鱼（Danio rerio）的脊椎动物模型系统，研究了GLUT3表达异常导致的葡萄糖转运和代谢障碍的细胞和分子机制。胚胎脑发育以剂量依赖性方式被破坏，导致异常脑器官发生的表型，与胚胎生长受限和细胞凋亡增加相关。通过提供外源性GLUT3 mRNA实现了对morphant表型的拯救。我们的结论是，GLUT3是至关重要的脑器官发生和胚胎生长。GLUT3的破坏是导致胚胎生长受限至死亡和小头畸形神经细胞凋亡的表型谱的原因。(C)2014爱思唯尔公司All rights reserved.
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. (C) 2014 Elsevier Inc. All rights reserved.