DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. Here, we test the function of DAN, a BMP antagonist we detected by analysis of chick cranial mesoderm. Our analysis shows that, pri...

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Hauptverfasser: McLennan, R, Bailey, C, Schumacher, LJ, Teddy, J, Morrison, J, Kasemeier-Kulesa, J, Wolfe, L, Gogol, M, Baker, R, Maini, PK, Kulesa, P
Format: Journal article
Veröffentlicht: Rockefeller University Press 2017
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author McLennan, R
Bailey, C
Schumacher, LJ
Teddy, J
Morrison, J
Kasemeier-Kulesa, J
Wolfe, L
Gogol, M
Baker, R
Maini, PK
Kulesa, P
author_facet McLennan, R
Bailey, C
Schumacher, LJ
Teddy, J
Morrison, J
Kasemeier-Kulesa, J
Wolfe, L
Gogol, M
Baker, R
Maini, PK
Kulesa, P
author_sort McLennan, R
collection OXFORD
description Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. Here, we test the function of DAN, a BMP antagonist we detected by analysis of chick cranial mesoderm. Our analysis shows that, prior to neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells, in vivo and in vitro respectively. In vivo loss-of-function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Taken together, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with inhibition of BMP signaling.
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spelling oxford-uuid:f4aec651-89db-4ea9-b93c-0adbe5ffb6ee2022-03-27T12:21:39ZDAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f4aec651-89db-4ea9-b93c-0adbe5ffb6eeSymplectic Elements at OxfordRockefeller University Press2017McLennan, RBailey, CSchumacher, LJTeddy, JMorrison, JKasemeier-Kulesa, JWolfe, LGogol, MBaker, RMaini, PKKulesa, PNeural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. Here, we test the function of DAN, a BMP antagonist we detected by analysis of chick cranial mesoderm. Our analysis shows that, prior to neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells, in vivo and in vitro respectively. In vivo loss-of-function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Taken together, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with inhibition of BMP signaling.
spellingShingle McLennan, R
Bailey, C
Schumacher, LJ
Teddy, J
Morrison, J
Kasemeier-Kulesa, J
Wolfe, L
Gogol, M
Baker, R
Maini, PK
Kulesa, P
DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion
title DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion
title_full DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion
title_fullStr DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion
title_full_unstemmed DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion
title_short DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion
title_sort dan nbl1 promotes collective neural crest migration by restraining uncontrolled invasion
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