Abstract
BackgroundStromal derived factor (SDF-1), an alpha chemokine, is a widely known chemoattractant in the immune system. A growing body of evidence now suggests multiple regulatory roles for SDF-1 in the developing nervous system.ResultsTo 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.ConclusionResults from this study show that SDF-1 regulates distinct cortical cell populations in vitro.
Highlights
Stromal derived factor (SDF-1), an alpha chemokine, is a widely known chemoattractant in the immune system
To investigate the role of Stromal derived factor-1 (SDF-1) signaling in cortical cell proliferation, rat embryonic day 17 (E17) primary cultures were exposed to a chronic treatment of chemokine medium (4–6 nM)
91% of the 5 bromodeoxyuridine (BrdU) labeled cells in control cultures were postmitotic compared to 81% after SDF-1 treatment (p < 0.01, n = 4 experiments), suggesting that the chemokine maintains the progenitors in proliferation
Summary
Stromal derived factor (SDF-1), an alpha chemokine, is a widely known chemoattractant in the immune system. A growing body of evidence suggests multiple regulatory roles for SDF-1 in the developing nervous system. Genetic mechanisms involving proneural genes Ngn1/2 and the homeodomain gene Pax have been implicated in the specification of pyramidal neurons. Proneural gene Mash 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. Chemokines are known to exert regulatory roles in the developing nervous system. Stromal derived factor (SDF-1), an alpha chemokine, has been identified in the developing and adult brain
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