Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsWoodham, Emma F
Paul, Nikki R
Spence, Heather J
Scribner, Michelle R
Marston, Daniel J
Hahn, Klaus M
Tait, Stephen W G
Brakebusch, Cord H
Insall, Robert H
Machesky, Laura M
MetadataShow full item record
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.
CitationCoordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. 2017, 27 (5):624-637 Curr. Biol.
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalCurrent biology : CB
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- The Arp2/3 complex is crucial for colonisation of the mouse skin by melanoblasts.
- Authors: Papalazarou V, Swaminathan K, Jaber-Hijazi F, Spence H, Lahmann I, Nixon C, Salmeron-Sanchez M, Arnold HH, Rottner K, Machesky LM
- Issue date: 2020 Nov 15
- Rac1 drives melanoblast organization during mouse development by orchestrating pseudopod- driven motility and cell-cycle progression.
- Authors: Li A, Ma Y, Yu X, Mort RL, Lindsay CR, Stevenson D, Strathdee D, Insall RH, Chernoff J, Snapper SB, Jackson IJ, Larue L, Sansom OJ, Machesky LM
- Issue date: 2011 Oct 18
- RhoA, Rac1, and Cdc42 differentially regulate αSMA and collagen I expression in mesenchymal stem cells.
- Authors: Ge J, Burnier L, Adamopoulou M, Kwa MQ, Schaks M, Rottner K, Brakebusch C
- Issue date: 2018 Jun 15
- Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs.
- Authors: Cleghorn WM, Bulus N, Kook S, Gurevich VV, Zent R, Gurevich EV
- Issue date: 2018 Jan
- Rho GTPases in embryonic development.
- Authors: Duquette PM, Lamarche-Vane N
- Issue date: 2014