Stromal derived factor-1 exerts differential regulation on distinct cortical cell populations in vitro

To investigate the role of SDF-1 signaling in the growth and differentiation of cortical cells, we performed numerous in vitro experiments, including gene chip and quantitative RT-PCR analysis. Using SDF-1 medium and AMD3100, a receptor antagonist, we demonstrate that the chemokine signaling regulates key events during early cortical development. First, SDF-1 signaling maintains cortical progenitors in proliferation, possibly through a mechanism involving connexin 43 mediated intercellular coupling. Second, SDF-1 signaling upregulates the differentiation of cortical GABAergic neurons, independent of sonic signaling pathway. Third, SDF-1 enables the elongation and branching of axons of cortical glutamatergic neurons. Finally, cortical cultures derived from CXCR4-/- mutants show a close parallel to AMD3100 treatment with reduced cell proliferation and differentiation of GABAergic neurons.Results from this study show that SDF-1 regulates distinct cortical cell populations in vitro.The cerebral cortex is primarily composed of glutamatergic pyramidal neurons of dorsal telencephalon and GABAergic interneurons that emanate from ventral telencephalon [1]. The generation of cortical neurons is a tightly orchestrated process that involves the commitment of multipotent stem cells to lineage-restricted progenitors, progression of progenitors to postmitotic neurons and their subsequent migration to correct layer positions. The molecular mechanisms that underlie many of these early events are being unraveled. Accordingly, genetic mechanisms involving proneural genes Ngn1/2 and the homeodomain gene Pax6 have been implicated in the specification of pyramidal neurons. Similarly, proneural gene Mash1 and homeodomain genes Dlx 1, 2 that are specific to basal ganglia are known to direct the specification of cortical interneurons [2].In addition to the intrinsic regulators, numerous extrinsic signals that influence the cortical progenitors and neurons have been identified. Among these,