Abstract
Activation of cAMP signaling pathway, along with its transcriptional factor CREB and coactivator CBP, are key determinants of neuronal differentiation. Our studies have revealed an integrative nuclear FGFR1 signaling (INFS) pathway by which extracellular signals and cAMP induce differentiation of proliferating fetal brain‐ or cord blood‐derived neuronal progenitor cells. Upon cell stimulation, FGF receptor‐1 (FGFR1) is released from ER membranes into the cytosol and translocates to cell nucleus where it blocks cell proliferation and induces neuronal differentiation. FGFR1 associates with the active nuclear centers of RNA synthesis and processing and activates structurally distinct neural‐specific genes and CBP. Our findings indicate that (1) INFS mediates activation of multigene program for neuronal growth/differentiation, and (2) FGFR1 serves as a nuclear matrix‐attached scaffold on which multifunctional protein complexes are dynamically assembled causing a coordinated local RNA pol II regulation and chromatin remodeling.
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