Chemokine-mediated migration of mesencephalic neural crest cells.
Clefts of the lip and/or palate are among the most prevalent birth defects affecting approximately 7000 newborns in the United States annually. Disruption of the developmentally programmed migration of neural crest cells (NCCs) into the orofacial region is thought to be one of the major causes of orofacial clefting. Signaling of the chemokine SDF-1 (Stromal Derived Factor-1) through its specific receptor, CXCR4, is required for the migration of many stem cell and progenitor cell populations from their respective sites of emergence to the regions where they differentiate into complex cell types, tissues and organs. In the present study, "transwell" assays of chick embryo mesencephalic (cranial) NCC migration and ex ovo whole embryo "bead implantation" assays were utilized to determine whether SDF-1/CXCR4 signaling mediates mesencephalic NCC migration. Results from this study demonstrate that attenuation of SDF-1 signaling, through the use of specific CXCR4 antagonists (AMD3100 and TN14003), disrupts the migration of mesencephalic NCCs into the orofacial region, suggesting a novel role for SDF-1/CXCR4 signaling in the directed migration of mesencephalic NCCs in the early stage embryo.
University of Louisville, Birth Defects Center, Department of Molecular, Cellular and Craniofacial Biology, ULSD, 501 S. Preston St., Suite 350, Louisville, KY 40202, USA. f0rezz01@louisville.edu
Francine
F
Rezzoug
Ratnam S
RS
Seelan
Vasker
V
Bhattacherjee
Robert M
RM
Greene
M Michele
MM
Pisano
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D002642:Chick Embryo; D002645:Chickens; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008636:Mesencephalon / Q000166:cytology*; D009432:Neural Crest / Q000166:cytology* / Q000187:drug effects*; D054259:Neural Tube / Q000166:cytology / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D054377:Chemokine CXCL12; D010455:Peptides; D019718:Receptors, CXCR4; C488289:TN14003