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Inhibition of Cranial Neural Crest Adhesion in Vitro and Migration in Vivo Using Integrin Antisense Oligonucleotides

Kil, Sung H. and Lallier, Thomas and Bronner-Fraser, Marianne (1996) Inhibition of Cranial Neural Crest Adhesion in Vitro and Migration in Vivo Using Integrin Antisense Oligonucleotides. Developmental Biology, 179 (1). pp. 91-101. ISSN 0012-1606. doi:10.1006/dbio.1996.0243.

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Although it is well-established that β_1 integrins play a functional role in the migration of cranial neural crest cells, little is known about the number or importance of their associated α subunits. Here, we have utilized antisense oligonucleotides (aONs) against various mammalian integrin α subunits to functionally “knock out” integrinsin vitro and in vivo. First, we examined the attachment in vitro of cranial neural crest cells to fibronectin and laminin in the presence of antisense or reversed-sense oligonucleotides using a quantitative adhesion assay. We found three α integrin aONs that blocked attachment to fibronectin substrates only, one that blocked attachment to laminin substrates only, and one that blocked attachment to both fibronectin and laminin. As expected, an aON to chick β_1 integrin reduced attachment to both fibronectin and laminin substrates. These results suggest that there are three or more functionally distinct integrin heterodimers on avian cranial neural crest cells. Second, we examined the ability of aONs against various α integrin subunits to perturb cranial neural crest migrationin vivoby injecting the oligonucleotides into the cranial mesenchyme through which neural crest cells migrate. Those α aONs that inhibited cell attachment in vitro also caused neural crest and/or neural tube abnormalities after injection in vivo.In addition, two aONs that had no effect in vitro did affect emigration of neural crest cells in vivo. Immunoprecipitations revealed that some integrin subunits were depleted after treatment with antisense but not reversed-sense oligonucleotides both in vivo and in vitro. The results suggest that integrin α subunits are required for cranial neural crest cell attachment and emigration.

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Lallier, Thomas0000-0001-6577-6676
Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 1996 Academic Press, Inc. Received 8 May 1996, Accepted 16 July 1996, Available online 7 May 2002. We thank Drs. Catherine Krull and Ben Murray for critical reading of the manuscript. This work was supported by USPHS HD-15527 to M.B.-F.
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Official Citation:Sung H. Kil, Thomas Lallier, Marianne Bronner-Fraser, Inhibition of Cranial Neural Crest Adhesion in Vitro and Migration in Vivo Using Integrin Antisense Oligonucleotides, Developmental Biology, Volume 179, Issue 1, 10 October 1996, Pages 91-101, ISSN 0012-1606,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65585
Deposited By: Ruth Sustaita
Deposited On:22 Mar 2016 17:59
Last Modified:23 Dec 2022 16:51

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