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Brain development: Changing cortex, changing glycans

Working out the differences in cell surface glycosylation between different organs and at different stages of development is a primary goal of glycomics. This is a complex task as glycosyltransferase genes are often poorly expressed, and glycans in vivo do not always mirror transferase gene expression patterns. For this reason researchers use a double-tracked approach of expression profiling and chemical glycan analysis to identify the differences in glycosylation. The design of a glycogene chip derived from a commercially available cDNA microarray has aided expression profiling between different tissue types. Now, a new study by Ishii et al. in Glycobiology describes a different cDNA array design that allows the detection of changes in glycosylation during the development of the mouse cortex.

Ishii et al. compared the cerebral cortices from mice at five time points during embryonic and neonatal development, and found that fluorometrical analysis was not sufficiently sensitive to reveal expression level differences between the various cortex samples. Additionally, some genes important for N-glycan biosynthesis were missing from the original cDNA glycochip. To work around this Ishii et al. designed a new glycogene macroarray using mouse and homologous human sequences that allows transferase expression to be monitored with autoradiography. The authors used this new array to show that glycogene expression in the mouse cortex changed by as much as four-fold during development. 2,8–sialyltransferase II was among the genes that showed a change in expression. It reached its maximum level in the cortex of the newborn mouse, and almost completely disappeared 12 weeks after birth.

The authors were able to identify 70% of the total N–linked sugar chains using high pressure liquid chromatography. Lewis X glycans — which contain a terminal 1-3 fucose — increased two-fold during development; mice lacking the corresponding fucosyltransferase have recently been shown to have severe behavioral impairments. Ishii et al. also observed that the amounts of N-glycans containing a high number of mannose residues changed drastically in the examined period of time. This lends support to the hypothesis that specific levels of N-glycans may influence the formation of synapses during cortex development. By using both expression quantification and N-glycan analysis, the authors were able to construct an enzymatic pathway for N–glycan formation in the mouse brain.

This study by Ishii et al. has elucidated the changes in glycosylation that occur during development. Further refinement of the genetic profiling described in this study might provide better resolution of the expression screens, thus allowing cell subpopulation glycosylation analysis in specific organs.

Author: Mirko von Elstermann