Glial cells modulate heparan sulfate proteoglycan (HSPG) expression by neuronal precursors during early postnatal cerebellar development

Cerebellum controls motor coordination, balance, eye movement, and has been implicated in memory and addiction. As in other parts of the CNS, correct embryonic and postnatal development of the cerebellum is crucial for adequate performance in the adult. Cellular and molecular defects during cerebellar development can lead to severe phenotypes, such as ataxias and tumors. Knowing how the correct development occurs can shed light into the mechanisms of disease. Heparan sulfate proteoglycans are complex molecules present in every higher eukaryotic cells and changes in their level of expression as well as in their structure lead to drastic functional alterations. This work aimed to investigate changes in heparan sulfate proteoglycans expression during cerebellar development that could unveil control mechanisms. Using real time RT-PCR we evaluated the expression of syndecans, glypicans and modifying enzymes by isolated cerebellar granule cell precursors, and studied the influence of soluble glial factors on the expression of those genes. We evaluated the possible involvement of Runx transcription factors in the response of granule cell precursors to glial factors. Our data show for the first time that cerebellar granule cell precursors express members of the Runx family and that the expression of those genes can also be controlled by glial factors. Our results also show that the expression of all genes studied vary during postnatal development and treatment of precursors with glial factors indicate that the expression of heparan sulfate proteoglycan genes as well as genes encoding heparan sulfate modifying enzymes can be modulated by the microenvironment, reflecting the intricate relations between neuron and glia.

Research highlights▶ Expression of syndecans and glypicans by neuronal precursors varies during early postnatal cerebellar development. ▶Expression of heparan sulfate sulfotransferases and extracellular sulfatases is also regulated during development. ▶ Soluble factors secreted by glial cells modulate axonal outgrowth and gene expression by cerebellar neuronal precursors. ▶ The expression of the transcription factors RUNXs is modulated by glial factors and correlates to syndecan expression.