Molecular and morphological characterization of caudal neural tube defects in embryos of diabetic swiss albino mice

Abstract

Embryos from diabetic mice exhibit several forms of neural tube defects including non-closure of the caudal neural tube. In the present study, embryos collected at embryonic day 11.5 from diabetic pregnancies displayed open neural tube with architectural disruption of the surrounding tissues. The percentage of proliferating cells was found to be increased in the dorsal and ventral domains of the spinal neural tube of embryos from diabetic mice, indicating a defect in the precise timing of cell-cycle exit. We have analyzed the development of various cell types including motoneurons, interneurons, oligodendrocytes and migrating neurons as well as radial glial cells in the open neural tube using specific molecular markers. Immunofluorescence results revealed a significantly reduced number of Pax2+ interneurons and increased number of Isl-1+ motoneurons as well as Olig2+ oligodendrocytes in the caudal neural tube of embryos from diabetic mice as compared to controls. In addition, these embryos exhibited a decreased number of doublecortin positive migrating neurons and Glast/Blbp positive radial glial cells with shortened processes in the neural tube. Expression levels of several developmental control genes involved in generation of different neuronal cell types (such as Shh, Ngn, Ngn2, Ascl1) were also found to be altered in the caudal neural tube of embryos from diabetic mice.