title: N-cadherin and Cx43alpha1 gap junctions modulates mouse neural crest cell motility via distinct pathways.
abstract: Our previous studies showed an essential role for connexin 43 or alpha1 connexin (Cx43alpha1) gap junctions in the modulation of neural crest cell motility. Cx43alpha1 gap junctions and N-cadherin containing adherens junctions are expressed in migrating cardiac neural crest cells. Analysis of the N-cadherin knockout (KO) mouse model revealed that N-cadherin is essential for gap junction mediated dye coupling but not for expression of Cx43alpha1 gap junctions in neural crest cells. Time lapse videomicroscopy and motion analysis showed that the motility of N-cadherin KO neural crest cells were altered, but the motility changes differed compared to Cx43alpha1 KO neural crest cells. These observations suggest that the role of N-cadherin in cell motility is not simply mediated via the modulation of Cx43alpha1 mediated cell-cell communication. This was confirmed by a parallel analysis of wnt-1 deficient neural crest cells, which also showed a reduction in dye coupling, and yet no change in cell motility. Analysis of p120 catenin (p120ctn), an Amardillo family protein known to play a role in cell motility, showed that it is colocalized with N-cadherin and Cx43alpha1 in migrating neural crest cells. This subcellular distribution was altered in the N-cadherin and Cx43alpha1 KO neural crest cells. Given these results, we propose that N-cadherin and Cx43alpha1 may modulate neural crest cell motility by engaging in a dynamic cross-talk with the cell's locomotory apparatus through p120ctn signaling.
authors.affiliation: Biology Department, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: W E
authors.initials: WE
authors.lastname: Li
authors.forename: G Y
authors.initials: GY
authors.lastname: Huang
authors.forename: R
authors.initials: R
authors.lastname: Meyer
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: M P
authors.initials: MP
authors.lastname: Thomas
authors.forename: G L
authors.initials: GL
authors.lastname: Radice
authors.forename: C W
authors.initials: CW
authors.lastname: Lo
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D018031:Connexin 43 / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D017629:Gap Junctions / Q000378:metabolism; D006321:Heart / Q000196:embryology; D051379:Mice; D018715:Microscopy, Video; D009432:Neural Crest / Q000166:cytology / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013997:Time Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D018031:Connexin 43; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse