The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors.
Chemokines and their receptors are essential for the development and organization of the hematopoietic/lymphopoietic system and have now been shown to be expressed by different types of cells in the nervous system. In mouse embryos, we observed expression of the chemokine (CXC motif) receptor 4 (CXCR4) by neural crest cells migrating from the dorsal neural tube and in the dorsal root ganglia (DRGs). Stromal cell-derived factor-1 (SDF-1), the unique agonist for CXCR4, was expressed along the path taken by crest cells to the DRGs, suggesting that SDF-1/CXCR4 signaling is needed for their migration. CXCR4 null mice exhibited small and malformed DRGs. Delayed migration to the DRGs was suggested by ectopic cells expressing tyrosine receptor kinase A (TrkA) and TrkC, neurotrophin receptors required by DRG sensory neuron development. In vitro, the CXCR4 chemokine receptor was upregulated by migratory progenitor cells just as they exited mouse neural tube explants, and SDF-1 acted as a chemoattractant for these cells. Most CXCR4-expressing progenitors differentiated to form sensory neurons with the properties of polymodal nociceptors. Furthermore, DRGs contained a population of progenitor cells that expressed CXCR4 receptors in vitro and differentiated into neurons with a similar phenotype. Our findings indicate an important role for SDF-1/CXCR4 signaling in directing the migration of sensory neuron progenitors to the DRG and potentially in other aspects of development once the DRGs have coalesced.
Belmadani
Abdelhak
A
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Tran
Phuong B
PB
Ren
Dongjun
D
Assimacopoulos
Stavroula
S
Grove
Elizabeth A
EA
Miller
Richard J
RJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001596:Benzylamines; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D000080027:Cyclams; D004268:DNA-Binding Proteins / Q000378:metabolism; D004347:Drug Interactions; D004622:Embryo, Mammalian; D016257:Fura-2 / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006609:High Mobility Group Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055748:SOXB1 Transcription Factors; D013002:Somatomedins / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D050819:Transcription Factor Brn-3A / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D000906:Antibodies; D001596:Benzylamines; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D004268:DNA-Binding Proteins; D006571:Heterocyclic Compounds; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; C109220:NBPhox protein; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C494189:Pou4f1 protein, mouse; D020800:Receptor, Nerve Growth Factor; D019718:Receptors, CXCR4; D055748:SOXB1 Transcription Factors; D013002:Somatomedins; C098693:Sox1 protein, mouse; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D011189:Potassium Chloride; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D002211:Capsaicin; D001920:Bradykinin; C088327:plerixafor; D002118:Calcium; D016257:Fura-2