Thrombospondin-1 and neural crest cell migration.
Using a monoclonal antibody raised against human platelet thrombospondin, we found anti-thrombospondin immunoreactivity in the extracellular matrix of avian embryos, coincident with the ventral pathways followed by trunk neural crest cells. To confirm that the antibody recognized thrombospondin-1 and to determine the tissue of origin of the thrombospondin matrix, a thrombospondin-1 cRNA probe was used for whole mount in situ hybridization. This probe revealed thrombospondin-1 mRNAs in the developing myotome before and during neural crest cell migration. The effect of thrombospondin-1 on neural crest cell migration, morphology, and adhesion was assayed in vitro. Quail trunk neural crest cells cultured on 4 microg/ml of thrombospondin-1 migrate at 1.14 +/- 0.54 microm/min, which is significantly greater than the rate of cell migration on tissue culture plastic. Using a shaker-based adhesion assay, a significantly greater number of neural crest cells remain attached to dishes coated with 4 microg/ml of thrombospondin-1 than to tissue culture plastic alone. The number of neural crest cells that remain attached to 4 microg/ml of thrombospondin-1 is similar to the number that remain attached to dishes coated with 10 microg/ml of fibronectin. These observations indicate that neural crest cells migrate through a thrombospondin-filled extracellular matrix, and that thrombospondin-1 promotes neural crest cell migration and adhesion. Thus, thrombospondin-1 is the first somite-derived extracellular matrix molecule with properties consistent with a role in the promotion of migration into the anterior somite, as opposed to the repulsion of neural crest cells from the posterior half of the somite.
Tucker
R P
RP
Department of Cell Biology and Human Anatomy, University of California at Davis School of Medicine, 95616, USA. rptucker@ucdavis.edu
Hagios
C
C
Chiquet-Ehrismann
R
R
Lawler
J
J
Hall
R J
RJ
Erickson
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009432:Neural Crest / Q000196:embryology*; D019700:Thrombospondin 1 / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D005353:Fibronectins; D019700:Thrombospondin 1; D001973:Bromodeoxyuridine