Show simple item record

dc.contributor.authorWoodham, Emma F
dc.contributor.authorPaul, Nikki R
dc.contributor.authorTyrrell, Benjamin
dc.contributor.authorSpence, Heather J
dc.contributor.authorSwaminathan, Karthic
dc.contributor.authorScribner, Michelle R
dc.contributor.authorGiampazolias, Evangelos
dc.contributor.authorHedley, Ann
dc.contributor.authorClark, William
dc.contributor.authorKage, Frieda
dc.contributor.authorMarston, Daniel J
dc.contributor.authorHahn, Klaus M
dc.contributor.authorTait, Stephen W G
dc.contributor.authorLarue, Lionel
dc.contributor.authorBrakebusch, Cord H
dc.contributor.authorInsall, Robert H
dc.contributor.authorMachesky, Laura M
dc.date.accessioned2017-04-07T08:25:19Z
dc.date.available2017-04-07T08:25:19Z
dc.date.issued2017-03-06
dc.identifier.citationCoordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. 2017, 27 (5):624-637 Curr. Biol.en
dc.identifier.issn1879-0445
dc.identifier.pmid28238662
dc.identifier.doi10.1016/j.cub.2017.01.033
dc.identifier.urihttp://hdl.handle.net/10033/620889
dc.description.abstractThe individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleCoordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCurrent biology : CBen
refterms.dateFOA2018-06-12T17:59:20Z
html.description.abstractThe individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.


Files in this item

Thumbnail
Name:
Publisher version
Thumbnail
Name:
Woodham et al.pdf
Size:
12.13Mb
Format:
PDF
Description:
Open Access article

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by-nc-sa/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/