Cdon promotes neural crest migration by regulating N-cadherin localization

Davalyn R. Powell; Jason S. Williams; Laura Hernandez-Lagunas; Ernesto Salcedo; Jenean H. O'Brien; Kristin Bruk Artinger

doi:10.1016/j.ydbio.2015.07.025

Cdon promotes neural crest migration by regulating N-cadherin localization

Davalyn R. Powell, Jason S. Williams, Laura Hernandez-Lagunas, Ernesto Salcedo, Jenean H. O'Brien, Kristin Bruk Artinger

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.

Original language	English (US)
Pages (from-to)	289-299
Number of pages	11
Journal	Developmental Biology
Volume	407
Issue number	2
DOIs	https://doi.org/10.1016/j.ydbio.2015.07.025
State	Published - Nov 15 2015
Externally published	Yes

Bibliographical note

Funding Information:
We thank past and present members of the Artinger lab, especially Christy Cortez Rossi for help with some of the initial expression analyzes. We also thank Morgan Singleton for excellent fish care, Laura Hudish and Alex Blasky in the Appel lab for help with live cell imaging and Shh regents and analysis, Robert Krauss and Paola Bovolenta for cdon reagents and discussion of function, and Linda Barlow for insightful reading of this manuscript. MNCD2 antibody developed by M. Takeichi and H. Matsunami was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. This work is supported by the NIH NIDCR pre-doctoral fellowship F31DE022237 to D.R.P., and and NIH NIDCR grant R01DE017699 to K.B.A. and NIH NINDS P30NS048154 to the UC Denver zebrafish core facility .

Publisher Copyright:
© 2015 Elsevier Inc.

Keywords

Adhesion
Cell migration
Neural crest
Shh signaling
Zebrafish

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10.1016/j.ydbio.2015.07.025

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title = "Cdon promotes neural crest migration by regulating N-cadherin localization",

abstract = "Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.",

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note = "Funding Information: We thank past and present members of the Artinger lab, especially Christy Cortez Rossi for help with some of the initial expression analyzes. We also thank Morgan Singleton for excellent fish care, Laura Hudish and Alex Blasky in the Appel lab for help with live cell imaging and Shh regents and analysis, Robert Krauss and Paola Bovolenta for cdon reagents and discussion of function, and Linda Barlow for insightful reading of this manuscript. MNCD2 antibody developed by M. Takeichi and H. Matsunami was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. This work is supported by the NIH NIDCR pre-doctoral fellowship F31DE022237 to D.R.P., and and NIH NIDCR grant R01DE017699 to K.B.A. and NIH NINDS P30NS048154 to the UC Denver zebrafish core facility . Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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doi = "10.1016/j.ydbio.2015.07.025",

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AU - Williams, Jason S.

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AU - Salcedo, Ernesto

AU - O'Brien, Jenean H.

AU - Artinger, Kristin Bruk

N1 - Funding Information: We thank past and present members of the Artinger lab, especially Christy Cortez Rossi for help with some of the initial expression analyzes. We also thank Morgan Singleton for excellent fish care, Laura Hudish and Alex Blasky in the Appel lab for help with live cell imaging and Shh regents and analysis, Robert Krauss and Paola Bovolenta for cdon reagents and discussion of function, and Linda Barlow for insightful reading of this manuscript. MNCD2 antibody developed by M. Takeichi and H. Matsunami was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. This work is supported by the NIH NIDCR pre-doctoral fellowship F31DE022237 to D.R.P., and and NIH NIDCR grant R01DE017699 to K.B.A. and NIH NINDS P30NS048154 to the UC Denver zebrafish core facility . Publisher Copyright: © 2015 Elsevier Inc.

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N2 - Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.

AB - Neural crest cells (NCCs) are essential embryonic progenitor cells that are unique to vertebrates and form a remarkably complex and coordinated system of highly motile cells. Migration of NCCs occurs along specific pathways within the embryo in response to both environmental cues and cell-cell interactions within the neural crest population. Here, we demonstrate a novel role for the putative Sonic hedgehog (Shh) receptor and cell adhesion regulator, cdon, in zebrafish neural crest migration. cdon is expressed in developing premigratory NCCs but is downregulated once the cells become migratory. Knockdown of cdon results in aberrant migration of trunk NCCs: crestin positive cells can emigrate out of the neural tube but stall shortly after the initiation of migration. Live cell imaging analysis demonstrates reduced directedness of migration, increased velocity and mispositioned cell protrusions. In addition, transplantation analysis suggests that cdon is required cell-autonomously for directed NCC migration in the trunk. Interestingly, N-cadherin is mislocalized following cdon knockdown suggesting that the role of cdon in NCCs is to regulate N-cadherin localization. Our results reveal a novel role for cdon in zebrafish neural crest migration, and suggest a mechanism by which Cdon is required to localize N-cadherin to the cell membrane in migratory NCCs for directed migration.

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Cdon promotes neural crest migration by regulating N-cadherin localization

Abstract

Bibliographical note

Keywords

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