For example, they allow the passage of low molecular weight molecules into the cell. Gap junction communication has been shown in glial and neuronal cells and recently Cx43 was shown to negatively modulate neuronal differentiation. Cx36 is also hypothesized to play a role in neuronal development, because its expression peaks in the inferior olive, cerebellum, striatum, hippocampus and cerebral cortex during the first 3 postnatal weeks, a period that WY 14643 abmole coincides with extensive inter-neuronal coupling. Importantly, during development Cx36 expression becomes restricted to neuronal cells, while Cx43 expression becomes restricted to astrocytes. Cx36 is expressed dynamically during murine embryonic development and it is switched on earlier than other Cxs. Expression is evident at E9.5 in the forebrain and expands into the midbrain as neurogenesis occurs. By E12.5 its expression pattern matches that of major morphogenetic boundaries within the brain and this elevated pattern of expression continues until P14. This bimodal pattern of neural expression correlates with two major periods of circuit formation and further indicates a role for Cx36 in the fine-tuning of neural development. Neural stem cells have been identified in both the developing and adult nervous systems. These cells are self-renewing and can give rise to neurons, astrocytes and oligodendrocytes in the central nervous system. Functional gap junction proteins have been identified in neural and embryonic stem cells and they are thought to play an important role in cell survival and differentiation. Current data suggests that widespread Cx expression is required for synchronizing and fine-tuning developing populations of cells and their expression is both spatially and temporally regulated. In this study we investigate the role Cx36 plays during neuronal differentiation from neural stem cells and lentiviral over expression and knockdown strategies demonstrated that neural differentiation is positively influenced by Cx36. In the developing brain, neurons and their positions are established and then glial and other cells are matched to the architecture of the network. Foetal neurospheres maintained in culture contain a mixture of multipotent and lineage restricted cell types that can be differentiated to give rise to neurons, astrocytes and oligodendrocytes. Differentiation in the brain and in neurosphere models is known to be governed via intrinsic pathways and via responses to extracellular cues and by cell-cell contact, all of which can be regulated by Cxs. However, Cx36 is the only Cx identified to be expressed in neurons. In this study we showed that shRNA vectors significantly reduce Cx36 protein expression and also inhibit GJIC. Additionally, altering Cx36 expression does not affect the growth of neurosphere cultures.