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A monoclonal antibody against a laminin-heparan sulfate proteoglycan complex perturbs cranial neural crest migration in vivo

Bronner-Fraser, Marianne and Lallier, Thomas (1988) A monoclonal antibody against a laminin-heparan sulfate proteoglycan complex perturbs cranial neural crest migration in vivo. Journal of Cell Biology, 106 (4). pp. 1321-1329. ISSN 0021-9525. PMCID PMC2114992. doi:10.1083/jcb.106.4.1321.

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INO (inhibitor of neurite outgrowth) is a monoclonal antibody that blocks axon outgrowth, presumably by functionally blocking a laminin-heparan sulfate proteoglycan complex (Chiu, A. Y., W. D. Matthew, and P. H. Patterson. 1986. J. Cell Biol. 103: 1382-1398). Here the effect of this antibody on avian neural crest cells was examined by microinjecting INO onto the pathways of cranial neural crest migration. After injection lateral to the mesencephalic neural tube, the antibody had a primarily unilateral distribution. INO binding was observed in the basal laminae surrounding the neural tube, ectoderm, and endoderm, as well as within the cranial mesenchyme on the injected side of the embryo. This staining pattern was indistinguishable from those observed with antibodies against laminin or heparan sulfate proteoglycan. The injected antibody remained detectable for 18 h after injection, with the intensity of immuno-reactivity decreasing with time. Embryos ranging from the neural fold stage to the 9-somite stage were injected with INO and subsequently allowed to survive for up to 1 d after injection. These embryos demonstrated severe abnormalities in cranial neural crest migration. The predominant defects were ectopic neural crest cells external to the neural tube, neural crest cells within the lumen of the neural tube, and neural tube deformities. In contrast, embryos injected with antibodies against laminin or heparan sulfate proteoglycan were unaffected. When embryos with ten or more somites were injected with INO, no effects were noted, suggesting that embryos are sensitive for only a limited time during their development. Immunoprecipitation of the INO antigen from 2-d chicken embryos revealed a 200-kD band characteristic of laminin and two broad smears between 180 and 85 kD, which were resolved into several bands at lower molecular mass after heparinase digestion. These results indicate that INO precipitates both laminin and proteoglycans bearing heparan sulfate residues. Thus, microinjection of INO causes functional blockage of a laminin-heparan sulfate proteoglycan complex, resulting in abnormal cranial neural crest migration. This is the first evidence that a laminin-heparan sulfate proteoglycan complex is involved in aspects of neural crest migration in vivo.

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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 1988 Rockefeller University Press. The Authors acknowledge that RUP will make the Article freely available to the public on RUP’s website after expiration of the Initial Publication Period, and that RUP intends to submit the Article to PubMed Central in accordance with PubMed Central’s requirements, where the Article will be released to the public after expiration of the Initial Publication Period. After the Initial Publication Period, RUP will grant to the public the non- exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license as described at and Received for publication 13 July 1987, and in revised form 17 December 1987. Published April 1, 1988. We thank Dr. Scott Fraser for helpful comments on the manuscript, and Georgia Guillory and Carmen Domingo for excellent technical assistance. This work was supported by U.S. Public Health Service Grant HD-15527 and by Basic Research Grant 1-896 from the March of Dimes. M. Bronner-Fraser is a Sloan Foundation Fellow.
Funding AgencyGrant Number
U.S. Public Health Service (USPHS)HD-15527
March of Dimes1-896
Alfred P. Sloan FoundationUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC2114992
Record Number:CaltechAUTHORS:20160516-080748233
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Official Citation:A monoclonal antibody against a laminin-heparan sulfate proteoglycan complex perturbs cranial neural crest migration in vivo. M Bronner-Fraser and T Lallier J Cell Biol 1988 106:1321-1329. Published April 1, 1988, doi:10.1083/jcb.106.4.1321
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:67095
Deposited By: Ruth Sustaita
Deposited On:16 May 2016 19:35
Last Modified:11 Nov 2021 00:27

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