Glypican-4 is a protein encoded by the gene GPC4 in humans. The Glypicans have one or two major heparin sulphate proteoglycans families. 6 glypicans have been known to exist in mammals. Glypicans play a major role in morphogenesis during development and have been known to regulate the Hedgehog cell signalling and Wnt pathways. They also regulate the signalling of bone morphogenic proteins and fibroblast growth factors.

 

Glypicans are expressed in varied amounts in different tissues during the various developmental stages. Heparin sulfate Glypican 4 is known to be highly expressed in the mouse embryonic stem cells. It is known to regulate and control the self-renewal through modulation of Wnt/Beta-Catenin signalling pathways.

 

In a study conducted by Fico et al, showed the mouse embryonic stem cells which carried a hypomorphic Gpc 4 allele demonstrated increased levels of differentiation into nuclear receptor related-1 protein and dopaminergic neurons expressing tyrosine hydroxylase. Unlike the wild-type cells, these differentiating Gpc 4 mutant cells showed high expression of dopamine transporter and DOPA decarboxylase.

 

Both these markers were expressed in dopaminergic neurons. Transplantation of these Gpc-4 hypomorphic cells in 6-ODHA Parkinson’s disease rat model showed an improvement in the motor behaviours. Thus, application of the Gpc-4 activity control can provide new strategies for reducing embryonic stem cells features and increase neuronal differentiation