Molecular and morphological characterization of neural tube defects in embryos of diabetic Swiss Albino mice

Wan Ting Loh, S. Thameem Dheen, Boran Jiang, S. Dinesh Kumar and Samuel S.W. Tay

Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Offprint requests to: S. Thameem Dheen and Samuel S.W. Tay, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD10, 4 Medical Drive, Singapore. e-mail: antstd@nus.edu.sg or anttaysw@nus.edu.sg


Summary. Background and Results: Embryos from diabetic mice exhibit several forms of neural tube defects, including non-closure of the 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 proliferation index. 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 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 the generation of different neuronal cell types (such as Shh, Ngn, Ngn2, Ascl1) were also found to be altered in the neural tube of embryos from diabetic mice.
Conclusions: Overall, the open neural tube in embryos of diabetic mice exhibits defects in the specification of different cell types, including motoneurons and interneurons, as well as glial cells along the dorsoventral axis of the developing spinal cord. Although these defects are associated with altered expression of several development control genes, the exact mechanisms by which maternal diabetes contributes to these changes remain to be investigated. Histol Histopathol 26, 965-978 (2011)

Key words: Maternal diabetes, Developmental genes, Motoneurons, Interneurons, Oligodendrocytes, Neural tube defect

DOI: 10.14670/HH-26.965