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

Author: 

McLennan, R
Bailey, C
Schumacher, L
Teddy, J
Morrison, J
Kasemeier-Kulesa, J
Wolfe, L
Gogol, M
Baker, R
Maini, P
Kulesa, P

Publication Date: 

15 August 2017

Journal: 

Journal of Cell Biology

Last Updated: 

2021-10-17T08:01:39.5+01:00

Issue: 

10

Volume: 

216

DOI: 

10.1083/jcb.201612169

page: 

3339-3354

abstract: 

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.

Symplectic id: 

709120

Submitted to ORA: 

Submitted

Publication Type: 

Journal Article