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


RESULTS
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.


CONCLUSIONS
Results from this study show that SDF-1 regulates distinct cortical cell populations in vitro.
Pritchett
James
J
1,124 Stopford Building, Faculty of Life Sciences, The University of Manchester, Manchester, UK. J.Pritchett@postgrad.manchester.ac.uk <J.Pritchett@postgrad.manchester.ac.uk>
Wright
Clare
C
Zeef
Leo
L
Nadarajah
Bagirathy
B
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D019718:Receptors, CXCR4 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; C515256:Cxcl12 protein, mouse; C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4