The capacity of embryonic stem cells (ES cells) to differentiate into neuronal cells represents a potential source for neuronal replacement and a model for studying factors controlling early stages of neuronal differentiation. Various molecules have been used to induce such differentiation but so far neuropeptides acting via G-protein coupled receptors have not yet been profoundly investigated. Since undifferentiated ES-cells express numerous G-coupled receptors which expression is increasing with time in culture, it suggest a prominent role of these receptors in the maintenance and development of ES cells. RT-PCR analyses of Ghrelin is proven to have a prominent effect on the growth and proliferation of the neural progenitor cells in the dorsal motor nucleus of the vagus (DMNV), but its effect on ES cells has not yet been investigated. MC4 receptor, which binds both alpha-MSH and AgRP is expressed by ES-cells but wheter it has a function on neuronal differentiation is unknown. Y1 and Y5 receptors of NPY have proven to have a significant role in maintaining the pluripotency of ES cells. These original data demonstrate that functional G-protein coupled receptors have a role on differentiation into a neuronal phenotype. It opens an exciting new field for neuropeptide regulation of tissue ontogenesis. Using a three-dimensional „minibrain” could reveal potential selective differentiation in the forming tissue. Since these neuropeptides often regulates each other’s expression in the adult brain, it would be interesting to see whether these regulation networks can form in vitro in a differentiating cell-culture. This would open new ways of studying the effect of neuropeptides on neural differentiation and synaptic network formation.