Global gene expression analysis of cranial neural tubes in embryos of diabetic mice.
Maternal diabetes causes congenital malformations in various organs including the neural tube in fetuses. In this study, we have analyzed the differential gene expression profiling in the cranial neural tube of embryos from diabetic and control mice by using the oligonucleotide microarray. Expression patterns of genes and proteins that are differentially expressed in the cranial neural tube were further examined by the real-time reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunohistochemistry. Proliferation index and apoptosis were examined by BrdU (5-bromo-2-deoxyuridine) labeling and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay, respectively. Embryos (E11.5) of diabetic pregnancies displayed distortion in neuroepithelia of the cranial neural tube. Microarray analysis revealed that a total of 390 genes exhibited more than twofold changes in expression level in the cranial neural tube of embryos from diabetic mice. Several genes involving apoptosis, proliferation, migration, and differentiation of neurons in the cranial neural tube were differentially expressed in embryos of diabetic pregnancy. In addition, maternal diabetes perturbed the development of choroid plexus and ventricular systems and reduced the production of proteins such as Ttr and Igf2 in the developing brain, indicating that these changes could impair the survival and proliferation of neuroepithelial cells and neurogenesis in embryos of diabetic mice. It is concluded that altered expression of a variety of genes involved in brain development is associated with cranial neural tube dysmorphogenesis that may subsequently contribute to intellectual impairment of the offspring of a diabetic mother.
Jiang
Boran
B
Molecular Neurobiology Laboratory, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Kumar
S Dinesh
SD
Loh
Wan Ting
WT
Manikandan
J
J
Ling
Eng-Ang
EA
Tay
Samuel S W
SS
Dheen
S Thameem
ST
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D001921:Brain / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000002:abnormalities / Q000473:pathology / Q000503:physiopathology; D048909:Diabetes Complications / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D054259:Neural Tube / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D009436:Neural Tube Defects / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D011247:Pregnancy; D013234:Stem Cells / Q000378:metabolism
D009419:Nerve Tissue Proteins