Global gene expression analysis of cranial neural tubes in embryos of diabetic mice

Abstract

A high frequency of pregnancy complications including perinatal mortality and congenital malformations including neural tube anomalies has been shown in women with diabetes mellitus. In this study, the molecular and morphological changes in cranial neural tubes of embryos from diabetic mice have been investigated. Morphological analysis revealed the impaired development of cranial neural tubes, particularly the telencephalon, diencephalon, and rhombencephalon as well as the choroid plexus (CP) in E11.5 embryos of diabetic mice. The neuroepithelia of the forebrain and hindbrain and ventricles appeared to be distorted and fused. The molecular changes were analyzed using oligonucleotide microarray which showed that 1613 genes were differentially expressed in cranial neural tubes of embryos from diabetic mice. Among these genes, about f 390 genes exhibiting greater than 2-fold changes have been placed into 9 main functional categories as follows: 1. metabolism (27.7%); 2. cellular physiological process (20.3%); 3. cell communication (12.1%); 4. morphogenesis (6.9%); 5. response to stimulus (3.8%); 6. cell death (2.3%); 7. cell differentiation (2.1%); 8. small subsets of genes (5.4%). In addition, maternal diabetes appeared to impair the development of CP which produces cerebrospinal fluid that determines the shape of the developing brain and transfers nutrients, proteins and other molecules required for neuroepithelial cell proliferation and neurogenesis during brain development. It is possible that these changes may impede further development of functional domains of the brain and subsequently contribute to intellectual impairment in the offspring of diabetic mothers.