Research Goal: The Reelin signaling pathway plays an important role in regulating neuronal cell positioning and synaptic plasticity during the development of the brain. Disabled-1 (Dab1) is a key adaptor in this pathway. Reelin binds to its receptors to induce tyrosine phosphorylation of Dab1 which modulates the Reelin signal to ensure precise neuronal positioning. The Dab1 gene is highly complex and conserved in vertebrates. Several alternately spliced Dab1 isoforms have been documented in mouse, human, chicken, lizard and zebrafish. Our lab has identified 11 Dab1 variants that are expressed at different developmental stages in mouse brain and retina. Our data indicate that different isoforms of Dab1 respond differentially to Reelin stimulation. Neuro-Oncological Ventral Antigen (Nova) is a neuron-specific RNA-binding protein that modulates the Dab1 alternative splicing. Hence, it might be interesting to see if Nova is involved in the control of Reelin-Dab1 signaling to modulate neuronal migration and synaptic plasticity. We will answer this question using P19 cell lines. P19 is a teratocarcinoma cell line that may undergo neuronal cell differentiation with retinoic acid. My goal is to conduct various knockdown and over-expression experiments to determine the role of Nova in modulating the Reelin-Dab1 signaling pathway.