The Reelin signaling pathway has been proven to play a critical role in human neural development, especially in the architectonic development of the central nervous system. Extracelltilar Reeiin binds to the Very Low Density Lipoprotein Receptor (VLDLR) or the Apolipoprotein -E Receptor Type 2 (ApoER2) on the neural cell membrane and then induces tyrosine phosphorylation· o( the adapter protein Disabled - 1 (Dab-1 ). The phosphorylated Dab-I then cross talk with Wnt pathway to regulate gene expression. Recent researches have shown the Reelin pathway, or more specifically, Dab 1 over expression inhibits Glycogen Synthase Kinase 3P (GSK-3P) of the Wnt pathway. Taken the effect that inhibition of GSK-3P frees and promotes the P-Catenin acumination in cell cytosol and nucleus, and demonstrated by recent researches, increased level of neuron differentiation of GSK-3 p inhibited cell, we suggest that Dab-1 's ability of inhibit GSK- 3P will also result in increase level of P-Catenin in the human neural stem cells (HNSC), thus inducing the HNSC cells to differentiate. Testing the HNSC cells separately with Reelin conditioned media treatment and Dab-1 over-expression show significant increasing of acumination of P-Catenin in cell nucleus. Furthermore, demonstrated by our studies, Dab-1 over-expression also increases the neuron differentiation in HNSCs.

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