Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin

Emma F. Woodham, Nikki R. Paul, Benjamin Tyrrell, Heather J. Spence, Karthic Swaminathan, Michelle R. Scribner, Evangelos Giampazolias, Ann Hedley, William Clark, Frieda Kage, Daniel J. Marston, Klaus M. Hahn, Stephen W.G. Tait, Lionel Larue, Cord H. Brakebusch, Robert H. Insall, Laura M. Machesky

Research output: Contribution to journalArticle

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Abstract

The 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.

LanguageEnglish (US)
Pages624-637
Number of pages14
JournalCurrent Biology
Volume27
Issue number5
DOIs
StatePublished - Mar 6 2017

Fingerprint

pseudopodia
Pseudopodia
skin (animal)
actin
adhesion
Actins
Skin
Adhesion
epidermis (animal)
Epidermis
mice
Myosin Type II
Null Lymphocytes
rho GTP-Binding Proteins
hair follicles
neural crest
Cytokinesis
melanocytes
Hair Follicle
Neural Crest

Keywords

  • actin
  • actin cytoskeleton
  • adhesion
  • Cdc42
  • cell motility
  • integrin
  • melanocyte
  • migration
  • myosin
  • Rho GTPases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Woodham, E. F., Paul, N. R., Tyrrell, B., Spence, H. J., Swaminathan, K., Scribner, M. R., ... Machesky, L. M. (2017). Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. Current Biology, 27(5), 624-637. DOI: 10.1016/j.cub.2017.01.033

Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. / Woodham, Emma F.; Paul, Nikki R.; Tyrrell, Benjamin; Spence, Heather J.; Swaminathan, Karthic; Scribner, Michelle R.; Giampazolias, Evangelos; Hedley, Ann; Clark, William; Kage, Frieda; Marston, Daniel J.; Hahn, Klaus M.; Tait, Stephen W.G.; Larue, Lionel; Brakebusch, Cord H.; Insall, Robert H.; Machesky, Laura M.

In: Current Biology, Vol. 27, No. 5, 06.03.2017, p. 624-637.

Research output: Contribution to journalArticle

Woodham, EF, Paul, NR, Tyrrell, B, Spence, HJ, Swaminathan, K, Scribner, MR, Giampazolias, E, Hedley, A, Clark, W, Kage, F, Marston, DJ, Hahn, KM, Tait, SWG, Larue, L, Brakebusch, CH, Insall, RH & Machesky, LM 2017, 'Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin' Current Biology, vol 27, no. 5, pp. 624-637. DOI: 10.1016/j.cub.2017.01.033
Woodham EF, Paul NR, Tyrrell B, Spence HJ, Swaminathan K, Scribner MR et al. Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. Current Biology. 2017 Mar 6;27(5):624-637. Available from, DOI: 10.1016/j.cub.2017.01.033
Woodham, Emma F. ; Paul, Nikki R. ; Tyrrell, Benjamin ; Spence, Heather J. ; Swaminathan, Karthic ; Scribner, Michelle R. ; Giampazolias, Evangelos ; Hedley, Ann ; Clark, William ; Kage, Frieda ; Marston, Daniel J. ; Hahn, Klaus M. ; Tait, Stephen W.G. ; Larue, Lionel ; Brakebusch, Cord H. ; Insall, Robert H. ; Machesky, Laura M./ Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin. In: Current Biology. 2017 ; Vol. 27, No. 5. pp. 624-637
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